Macular Degeneration - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

MACULAR DEGENERATION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES...

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MACULAR

DEGENERATION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Macular Degeneration: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84024-5 1. Macular Degeneration-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on macular degeneration. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON MACULAR DEGENERATION...................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Macular Degeneration .................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 59 The National Library of Medicine: PubMed ................................................................................ 60 CHAPTER 2. NUTRITION AND MACULAR DEGENERATION .......................................................... 107 Overview.................................................................................................................................... 107 Finding Nutrition Studies on Macular Degeneration............................................................... 107 Federal Resources on Nutrition ................................................................................................. 112 Additional Web Resources ......................................................................................................... 112 CHAPTER 3. ALTERNATIVE MEDICINE AND MACULAR DEGENERATION ................................... 117 Overview.................................................................................................................................... 117 The Combined Health Information Database............................................................................. 117 National Center for Complementary and Alternative Medicine................................................ 118 Additional Web Resources ......................................................................................................... 123 General References ..................................................................................................................... 126 CHAPTER 4. DISSERTATIONS ON MACULAR DEGENERATION ..................................................... 127 Overview.................................................................................................................................... 127 Dissertations on Macular Degeneration.................................................................................... 127 Keeping Current ........................................................................................................................ 128 CHAPTER 5. CLINICAL TRIALS AND MACULAR DEGENERATION ................................................ 129 Overview.................................................................................................................................... 129 Recent Trials on Macular Degeneration.................................................................................... 129 Keeping Current on Clinical Trials ........................................................................................... 145 CHAPTER 6. PATENTS ON MACULAR DEGENERATION ................................................................ 147 Overview.................................................................................................................................... 147 Patents on Macular Degeneration ............................................................................................. 147 Patent Applications on Macular Degeneration ......................................................................... 165 Keeping Current ........................................................................................................................ 194 CHAPTER 7. BOOKS ON MACULAR DEGENERATION .................................................................... 195 Overview.................................................................................................................................... 195 Book Summaries: Federal Agencies............................................................................................ 195 Book Summaries: Online Booksellers......................................................................................... 196 The National Library of Medicine Book Index ........................................................................... 198 Chapters on Macular Degeneration........................................................................................... 199 CHAPTER 8. MULTIMEDIA ON MACULAR DEGENERATION ......................................................... 201 Overview.................................................................................................................................... 201 Video Recordings ....................................................................................................................... 201 Bibliography: Multimedia on Macular Degeneration................................................................ 202 CHAPTER 9. PERIODICALS AND NEWS ON MACULAR DEGENERATION ...................................... 203 Overview.................................................................................................................................... 203 News Services and Press Releases.............................................................................................. 203 Newsletter Articles .................................................................................................................... 206 Academic Periodicals covering Macular Degeneration ............................................................. 207 CHAPTER 10. RESEARCHING MEDICATIONS................................................................................. 209 Overview.................................................................................................................................... 209 U.S. Pharmacopeia..................................................................................................................... 209 Commercial Databases ............................................................................................................... 210 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 213

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Overview.................................................................................................................................... 213 NIH Guidelines.......................................................................................................................... 213 NIH Databases........................................................................................................................... 215 Other Commercial Databases..................................................................................................... 218 APPENDIX B. PATIENT RESOURCES ............................................................................................... 219 Overview.................................................................................................................................... 219 Patient Guideline Sources.......................................................................................................... 219 Associations and Macular Degeneration ................................................................................... 225 Finding Associations.................................................................................................................. 226 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 229 Overview.................................................................................................................................... 229 Preparation................................................................................................................................. 229 Finding a Local Medical Library................................................................................................ 229 Medical Libraries in the U.S. and Canada ................................................................................. 229 ONLINE GLOSSARIES................................................................................................................ 235 Online Dictionary Directories ................................................................................................... 237 MACULAR DEGENERATION DICTIONARY ....................................................................... 239 INDEX .............................................................................................................................................. 315

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with macular degeneration is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about macular degeneration, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to macular degeneration, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on macular degeneration. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to macular degeneration, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on macular degeneration. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON MACULAR DEGENERATION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on macular degeneration.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and macular degeneration, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “macular degeneration” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Age-Related Macular Degeneration Source: Access. 17(7): 30-34. August 2003. Contact: Available from American Dental Hygienists' Association (ADHA). 444 North Michigan Avenue, Chicago, IL 60611. (312) 440-8900. E-mail: [email protected]. Website: www.adha.org. Summary: Age-related macular degeneration (AMD) is the most common cause of vision loss and blindness in people over age 65, and it can affect people at younger ages as well. The risk of developing AMD steadily increases with age. This article reviews the anatomy and function of the normal retina. The author also identifies the risk factors for AMD and its causes, as well as its diagnosis and treatment. A diagnosis of AMD means

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a significant decrease in vision, and, in some cases, complete blindness. The author discusses the issues of AMD patients' everyday activities, and reviews the communication skills that dental hygienists can use with low-vision individuals. The author notes that the ability to cope with AMD depends on how much vision is lost, how sudden or gradual the change is, the patient's pre-illness coping style, and, especially, the patient's support system. One side bar lists assistive devices for people with low vision; another provides the contact information for four resource organizations. 6 figures. 12 references.

Federally Funded Research on Macular Degeneration The U.S. Government supports a variety of research studies relating to macular degeneration. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to macular degeneration. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore macular degeneration. The following is typical of the type of information found when searching the CRISP database for macular degeneration: •

Project Title: ABCR, MACULAR DYSTROPHIES AND DEGENERATION Principal Investigator & Institution: Lupski, James; Professor; Molecular and Human Genetics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): We identified the causative role of either compound heterozygous or homozygous mutations of ABCR in classic autosomal recessive Stargardt's macular dystrophy. The ABCR gene (also known as ABCA4) encodes a photoreceptor-specific ATP-binding cassette transporter, which has been shown recently to transport retinal or a derivative thereof. ABCR mutations also have a role in some forms of retinitis pigmentosa and a large fraction of cone-rod dystrophy. Thus, ABCR is likely to be responsible for a substantial portion of diverse retinal pathologies. That some heterozygous ABCR mutations are associated with the multifactorial disorder Age-Related Macular Degeneration suggests an even more prominent role for ABCR in visual impairment. We and others have proposed a model, the "ABCR activity vs. retinal disease phenotype hypothesis," in which the severity of retinal dystrophic phenotype is inversely proportional to the residual fraction of ABCR wild-type activity. That is, an RP phenotype results from essentially zero ABCR activity associated with two null mutations, while a late-onset Stargardt's macular dystrophy results from a selected combination of mutations that retain substantial ABCR activity. In this model,

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

Studies

5

heterozygous ABCR mutations represent a dominant susceptibility locus for AMD. The common final pathophysiological pathway is influenced by how much A2E (a conjugate of retinaldehyde and phosphatidylethanolamine that appears to be transported by the "ABCR flippase" and is the major toxic constituent of lipofuscin that accumulates in the flecks of STGD patients and drusen of those with AMD) accumulates in the retinal pigment epithelium. Using an assay to assess protein expression and ATP-binding activity we will perform functional analyses of disease-associated ABCR mutations. Further, we will systematically investigate and classify synergistic effects and the functional consequences of complex alleles. We will also develop a novel transporter assay to directly evaluate ABCR transporter/flippase function and the effects of diseasecausing mutation. Functional analyses of ABCR and mutations in retinopathy patients will expand greatly our knowledge of normal ABCR function and the dysfunction resulting in retinal pathology. Understanding the molecular pathway involving ABCR opens new avenues for the predictive diagnosis of selected retinal diseases and may lead to novel prophylactic and interventional therapies for these devastating disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: AGE-INDUCED PHENOTYPE OF THE RETINAL PIGMENT EPITHELIUM Principal Investigator & Institution: Handa, James T.; Associate Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): While a number of genes have been postulated to be involved in age-related macular degeneration (AMD), the leading cause of blindness among the elderly in the US, a comprehensive mRNA phenotype of the retinal pigment epithelium (RPE) in vivo is at present unknown. Determination of an RPE mRNA phenotype could identify the genes critical to the development of AMD, identify markers of disease, and lead to new preventative and treatment strategies. Basal deposits in Bruch's membrane are an early recognizable change that occur prior to degeneration of the RPE and are a histopathological marker for AMD. Recently, our laboratory identified an age-dependent accumulation of advanced glycation end products (AGEs) in Bruch's membrane and basal deposits. AGEs are structures formed during the series of nonenzymatic reactions between sugars or other precursors, and long-lived proteins that alter the phenotype of a variety of cell types. Our laboratory has also recently shown that AGEs alter the expression of genes involved in matrix regulation, cell polarity, and apoptosis in RPE cells. Our long term goal is to define an extensive mRNA phenotype of the RPE in health and AMD which will in turn, yield insights into the pathogenesis of AMD. Specifically, we want to define the component of that phenotype which is regulated by AGEs. We hypothesize that the presence of AGEs in basal deposits is responsible for a switch in the phenotype of RPE cells that is consistent with alterations in matrix regulation, RPE cell polarity, and apoptosis. To test this hypothesis we ask 3 questions: 1. Are the mRNA phenotypes of macular RPE cells overlying basal deposits and normal Bruch's membrane different? 2. Does AGE modified matrix induce an RPE mRNA phenotype in vitro that is a subset of the phenotype expressed by RPE cells overlying basal deposits? 3. Is a subset of the AGE induced mRNA phenotype of RPE cells mediated by the Receptor for Advanced Glycation End products? To answer these questions we will use laser capture microdissection to obtain pure samples of RPE cells from tissue specimens for mRNA phenotyping by microarray analysis. We will also utilize an in vitro AGE-matrix system to determine what subset of genes is regulated by AGEs. This project hopes to establish

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an extensive mRNA phenotype of the RPE in both health and AMD, and define a subset of genes induced by AGEs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EVENTS

AGE-RELATED

MACULOPATHY:

COMPLEMENT-MEDIATED

Principal Investigator & Institution: Johnson, Lincoln V.; None; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2002; Project Start 01-AUG-1996; Project End 31-MAR-2006 Summary: (provided by applicant): The objective of the proposed studies is to test the hypothesis that the process of drusen formation is stimulated by complement-mediated inflammatory events involving retinal pigmented epithelial (RPE) cells. Drusen are extracellular deposits that form between the RPE and Bruch's membrane, and are a significant risk factor for age-related macular degeneration (AMD). In AMD, functional compromise and ultimately death of RPE cells as a consequence of drusen formation is thought to lead to secondary degeneration of retinal photoreceptor cells and visual loss. Studies of age-related human diseases that, like AMD, involve cellular degeneration and the formation of insoluble deposits (e.g., Alzheimer's disease, atherosclerosis and kidney glomerulonephritis) now implicate complement activation and inflammatory events as key elements in disease processes. Data that we generated during the prior application period strongly suggest that complement activation also plays an important role in the formation of ocular drusen. We observed that terminal complement complexes and complement regulatory molecules are present in drusen, as are molecules with potential complement-activating properties. Furthermore, our observations show that RPE cells overlying drusen exhibit a compromised molecular phenotype that is consistent with a well-characterized cellular response to complement attack. Thus, these observations suggest an AMD disease process that is consistent with that of other age-related human diseases. A process that involves a primary pathogenic or age-related stimulus, the effects of which are exacerbated by localized, self-perpetuating, complement-mediated tissue destruction and inflammatory sequelae that persist over decades. The studies proposed here will examine the hypothesis that complement-mediated events contribute both to the process of drusen formation, and to the functional compromise of drusenassociated RPE cells. The studies will target the following specific aims: (1) To determine if RPE cell compromise is the result of complement-mediated attack, (2) To characterize the nature of the complement-mediated processes involved in drusen formation, and (3) To examine RPE cell responses to complement attack utilizing an in vitro model system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANALYSIS OF HUMAN VMD2: A MODEL FOR RPE GENE REGULATION Principal Investigator & Institution: Zack, Donald J.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Adapted from Applicant's abstract): The long-term objective of this project is to better understand the molecular mechanisms that underlie retinal pigment epithelium (RPE)-specific gene expression. The RPE is important for the function and survival of retinal photoreceptors. Abnormalities in the RPE have been implicated in the pathogenesis of photoreceptor degeneration both in the RCS rat and in human agerelated macular degeneration (AMD), the leading cause of irreversible blindness in

Studies

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elderly Americans. In addition, mutations in RPD65, RLBP1, TIMP3, and VMD2, four genes that are specifically or preferentially expressed in the RPE, have been shown to cause Leber's Congenital Amaurosis (LCA), retinitis pigmentosa (RP), Sorsby's fundus dystrophy (SFD), and vitelliform macular dystrophy (Best's disease), respectively. However, despite the importance of the RPD, and the importance of genes that are specifically or preferentially expressed in the RPE, little is known about the molecular mechanisms that regulate RPE-specific gene expression. Therefore, the goal of this proposal is to begin elucidating such mechanisms using human VMD2 (Best's disease gene) as a model system. More specifically, the following questions will be addressed: What are the cis-acting DNA elements that regulate VMD2 expression? Do different RPE-specific genes share common regulatory elements? What are the trans-acting factors that bind to the DNA regulatory elements? Are mutations in RPE promoters and/or RPE transcription factors involved in human disease? For answering these questions, DNA elements in the promoter region of VMD2 will be identified by sequence comparison with the other RPE-specific promoters and by biochemical analysis using DNase I footprint and electrophoretic mobility shift (EMSA) assays. The promoter region of VMD2 will be functionally analyzed using a combination of transient transfection and transgenic mouse approaches. Finally, to clone and characterize cDNAs for the trans-acting that bind to the DNA regulatory elements in the VMD2 promoter, we will use the yeast one-hybrid approach with a human RPE cDNA library. Increased understanding of RPE gene regulation should help provide new insights into diseases involving abnormalities of RPE gene expression. In addition, the knowledge will be useful in the development of RPE-targeted gene therapy and the generation of transgenic mice with targeted expression of exogenous proteins to the RPD. Furthermore, since Best's disease shares some clinical and histological features with AMD, studies of human VMD2 expression may have important implications for understanding macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTI-ANGIOGENIC SIGNALING MOLECULES IN RETINAL CELLS Principal Investigator & Institution: Rahimi, Nader; Ophthalmology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: Angiogenesis, formation of new blood vessels from pre-existing vessels is a hallmark of many eye diseases such as age-related macular degeneration, proliferative diabetic retinopathy, retinopathy of prematurity and vascular glaucoma, which are among leading cause of visual loss in the USA and throughout the world. Vascular endothelial growth factor (VEGF), the major stimulator of angiogenesis, elicits its effect by binding to and activating two endothelial receptors namely VEGFR-1/FLK-1 and VEGFR-2/FLT-1. Although activation of VEGFR-2 has been demonstrated to be an essential requirement for induction of angiogenesis, the role of VEGFR-1 in angiogenesis is largely unknown. We will investigate the molecular mechanisms responsible for action of VEGFR-1, such as activation of signaling molecules or induction of immediate early genes (IEG) that might drive its anti-angiogenesis effects in endothelial cells. The significance of the results obtained from the proposed study lies in their potential to provide fundamental information on how VEGFR-1 communicates to control/restrain angiogenesis in endothelial cells. The importance of angiogenesis in ocular diseases is well recognized. our long-term goal is to begin to apply the information obtained from this project to the design of strategies to regulate angiogenesis in clinical settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Macular Degeneration

•

Project Title: ANTIOXIDANT METABOLISM IN CHLAMYDOMONAS Principal Investigator & Institution: Niyogi, Krishna K.; Plant and Microbial Biology; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Reactive oxygen species (ROS) are generated inevitably in cells of all aerobic organisms, from bacteria plants and animals. Coping with the potentially damaging consequences of ROS generation is a problem of broad biological significance. The involvement of excited and highly reactive intermediates in oxygenic photosynthesis poses unique problems for algae and plants with respect to the generation of ROS. The proposed research plan is focused on the question of how photosynthetic organisms prevent or minimize photo-oxidative damage caused by ROS. To dissect antioxidant defenses in the chloroplast, mutants of the unicellular green alga Chlamydomonas reinhardtii, have been isolated. Several mutants affect the metabolism of xanthophyll pigments, which have critical roles in photoprotection in all algae and plants. An npq1 lor1 double mutant, which is deficient in lutein and zeaxanthin, undergoes photooxidative bleaching in high light, presumably due to increased production and/or decreased quenching of ROS, especially singlet oxygen. The proposed research will examine the types of photo- oxidative damage and the responses of various antioxidant systems in npq1 lor1 cells. Isolation of the genes affected in the xanthophyll mutants will enable determination of the molecular basis for the mutant phenotypes and will provide a strong foundation for further genetic analysis, including isolation of suppressors of npq1 lor1. The generation and/or scavenging of other ROS is perturbed in another group of mutants, which will be characterized using a combination of molecular genetic, biochemical, and physiological approaches. Understanding the metabolism and function of xanthophylls and other antioxidants in algae and plants will provide insights into the important roles of these molecules in preventing age-related diseases such as macular degeneration in humans and will enable engineering of antioxidant metabolism in plants to benefit human nutrition and health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ANTIOXIDANT SYSTEMS AND AGE RELATED MACULAR DEGENERATION Principal Investigator & Institution: Sternberg, Paul W.; Thomas Aaberg Professor; Ophthalmology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-AUG-1989; Project End 31-JUL-2004 Summary: (Adapted from the applicant's abstract): This research program focuses on the hypotheses that age-related macular degeneration (ARMD) can result from oxidative injury to the retinal pigment epithelium (RPE) and that glutathione (GSH) may protect the retina and RPE cells from ARMD-associated with oxidative injury. Previous work has shown that there is a shift in blood plasma redox status to a more oxidized state with aging, placing all tissues at risk for age-related diseases; there also appears to be a more oxidized redox state in patients' with more advanced ARMD. In vitro studies suggest that oxidative injury-induced apoptotic cell death in RPE cells may involve mitochondrial damage. Further, dietary inducers can stimulate increased GSH synthesis leading to elevated intracellular GSH, with concomitant increased protection against oxidative injury. In this project, the investigators propose to answer the following questions which will test their hypotheses: (1) how redox status is associated with ARMD; (2) what mechanism is involved in shifting GSH redox status to a more oxidized state that affects RPE cell function; (3) whether one can modulate GSH synthetic

Studies

9

capacity in human RPE cells by controlling the rate-limiting enzyme for GSH synthesis; and (4) what mechanisms are involved in the redox regulation of apoptosis in cultured human RPE cells. Biochemical studies, including HPLC, viability studies, measures of RPE function, TUNEL assay and other assays for apoptosis, and assays for mitochondrial function, will evaluate human blood plasma samples, cultured human RPE cells, and experimental animals. These studies should increase our understanding of the pathogenesis of ARMD, while directly suggesting new treatment strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: APOPTOSIS IN RETINAL DETACHMENTS Principal Investigator & Institution: Zacks, David N.; Ophthalmology and Visual Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Retinal diseases such as retinal detachments and macular degeneration are a leading cause of vision loss and blindness in this country and around the world. Despite available surgical and medical treatments for these diseases, patients still experience a large amount of vision loss secondary to the disruption in nutritional support provided to the retina by the underlying tissues. This disruption causes death of the retina, and of the photoreceptor cells in particular. Apoptosis, or programmed cell death, has been implicated as the mechanism by which photoreceptor cells die, but the molecular mechanisms of activation, transduction and execution of the apoptotic cascade in retinal diseases are poorly understood. The main hypothesis of this research proposal is that photoreceptor cell death during retinal detachments and macular degeneration occurs via apoptosis. The research outlined in this application will use a newly developed rodent model of retinal detachments and molecular biologic and genetic techniques to gain new insight into apoptotic photoreceptor cell death. This will allow us to develop and test new neuroprotective therapies for improving visual outcomes in retinal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: ATHEROSCLEROSIS MACULOPATHY

AND

RISK

OF

AGE-RELATED

Principal Investigator & Institution: Cruickshanks, Karen J.; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2003 Summary: (Applicant's Abstract) The purpose of this epidemiologic study is to evaluate the association of markers of generalized atherosclerosis with the incidence of early and late stage age-related maculopathy in a population-based, nested incident case-control study. This proposal builds on the population-based studies of aging in Beaver Dam, WI: The Beaver Dam Eye Study (EY06594) and the Epidemiology of Hearing Loss Study (AG11099). Participants with incident early age-related maculopathy or incident latestage age-related maculopathy as determined from grading of standardized photographs taken at two examinations five years apart will be eligible as cases for this study. Participants without age-related maculopathy at the time of the 1 0-yr follow-up eye examination will be eligible as controls. Incident early cases will be frequencymatched by age and gender to controls using a two-to-one ratio of controls to cases. Incident late age-related maculopathy cases will be frequency-matched to controls by age and gender using a three-to-one ratio of controls to cases. Based on expected 5-yr

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Macular Degeneration

incidence rates and participation rates in both studies, we estimate that a total of 189 cases with incident early age-related maculopathy and 378 controls and 34 cases with incident late age-related maculopathy and 102 controls will be included in this study. Generalized atherosclerosis will be measured by intima-medial thickness and the presence of plaque in the carotid arteries. Stored videotapes of B mode ultrasound scans of the carotid arteries were obtained as of the Epidemiology of Hearing Loss Study, using a modification of the Atherosclerosis Risk in Communities Study protocol. These scans will be read, and measurements of the intima-medial thickness made, using the Atherosclerosis Risk in Communities ultrasound reading protocol. Age-related maculopathy is well-recognized to be the leading cause of blindness among older adults and a significant public health problem for older adults. As yet there is no way to prevent or effectively treat this disorder. This study will provide important epidemiologic information about the role of atherosclerosis in the etiology of age-related maculopathy. It takes advantage of an unique opportunity to evaluate this association by utilizing an existing population-based cohort with standardized assessments of the incidence of age-related maculopathy and standardized carotid artery ultrasound scans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: BIOCHEMISTRY AND PHARMACOLOGY OF THE MACULAR CAROTENOIDS Principal Investigator & Institution: Bernstein, Paul S.; Assistant Ophthalmology and Visual Scis; University of Utah Salt Lake City, Ut 84102

Professor;

Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: The human macula, the specialized region of the retina responsible for high resolution visual acuity, selectively accumulates two xanthophy11 carotenoids derived from the diet, lutein and zeaxanthin. Several recent epidemiological studies have demonstrated a strong inverse correlation between dietary intake of lutein and zeaxanthin and the risk of progression Age-Related Macular Degeneration (AMD) the leading cause of blindness among the elderly in the United States. It is thought that the macular carotenoids protect against least-induced damage to the retina by filtering out damaging wavelengths of light and by acting as antioxidants. The biochemical mechanisms that mediate the selective uptake, concentration, and stabilization of the macular carotenoids are unknown. In lower animals, such as lobsters and cyanobacteria, specialized carotenoid-binding proteins perform these tasks. It is hypothesized that comparable carotenoid-binding proteins may have a similar role in the human macula. A major goal of this project is to understand the biochemical processes responsible for the specific deposition of lutein and zeaxanthin the macula, with special emphasis on the search for potential carotenoid-binding proteins. This project will also investigate the properties of carotenoid- protein and carotenoid-lipid interactions through quantitative binding studies and various spectroscopic methods, including resonance Raman spectroscopy, in model systems and in intact retinal tissue. The experiments of this proposal may provide new insights into the biochemical basis of the specific uptake lutein and zeaxanthin into the macula. Derangements of the mechanisms of uptake and stabilization of the macular carotenoids could have profound impact on the progression of AMD and inherited retinal dystrophies. Anticipated interventional clinical studies may be able to take advantage of the specific uptake systems to increase the level of macular carotenoid pigment and perhaps retard or prevent the progressive blindness produced by these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BIOCHEMISTRY OF THE RETINA SPECIFIC TRANSPORTER ABCR/RIM Principal Investigator & Institution: Nathans, Jeremy H.; Professor; Molecular Biology and Genetics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The goal of this research program is to develop an in vitro assay for the functional characterization of the retina-specific ABC transporter, ABCR/RIM. Mutations in the gene encoding ABCR/RIM are responsible for Stargardt disease (STGD), an autosomal recessive early onset form of macular degeneration, and have also been reported in a subset of patients with age related macular degeneration (AMD). Unpublished data implicate other mutations in this gene in some cases of autosomal recessive retinitis pigmentosa (RP). We aim to (1) identify the transported substrate and (2) develop methods for producing recombinant human ABCR/RIM that can be used to test the effect of mutations on the structure, function, and stability of this protein. Identifying the transported molecule(s) may reveal new compounds or new roles for known compounds. Determining whether the transported molecule is transported in conjunction with specific binding proteins, and studying its synthesis, degradation, and processing may lead both to the identification of additional candidate genes for retinal diseases, and to the identification of additional targets for drug development. Production of a large number of different ABCR/RIM proteins, each carrying a mutation found in humans with STGD, AMD, or RP will allow us to determine the biochemical defect in each case, and will allow a correlation to be drawn between the clinical characteristics of the affected subjects and the biochemical defects resulting from the mutations they carry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BONE MARROW-DERIVED STEM CELL TRANSPLANTATION TO RETINA Principal Investigator & Institution: Mcloon, Steven C.; Professor; Neuroscience; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Degeneration of retinal photoreceptor neurons, such as that seen in age-related macular degeneration (AMD), is the most common cause of blindness in the United States. There are compelling reasons to believe that subretinal cell transplantation could be used to replace missing photoreceptor neurons. No effective and practical source of cells for transplantation is currently available. The goal of this project is to develop cells to be used for transplantation to replace photoreceptor neurons in AMD and related diseases. Bone marrow-derived stem cells offer numerous advantages over other cell types as a possible source of donor cells. These cells can differentiate into neurons. They are readily available, and if used for autologous transplantation to the retina, they would not have the same immunological consequences inherent in the use of other cell types. To our knowledge, no other laboratories are investigating bone marrow-derived stem cells for transplantation to the retina. At this time, there is no evidence that bone marrow-derived stem cells can differentiate into retinal neurons. The specific aim of this preliminary investigation is to determine conditions that would allow these cells to differentiate as photoreceptor neurons or other retinal cell types. The study has three sequential steps. First, treat GFPlabeled, bone marrow-derived stem cells in ways likely to induce the photoreceptor phenotype. This includes culturing cells in factors such as FGF-2, EGF, retinoic acid,

12

Macular Degeneration

sonic hedgehog and taurine, and/or transfecting the cells with a gene for the photoreceptor cell specific transcription factor, Crx. Second, co-culture treated bone marrow-derived stem cells with embryonic retina or transplant the cells to the subretinal space in animals depleted of photoreceptor cells. Third, assess histologically the differentiation of bone marrow-derived stem cells in the retinal co-cultures or after transplantation to the retina by determining their laminar distribution in the host retina and by immunohistochemistry with antibodies specific to retinal cell types. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHARACTERIZATION OF RPE MONOLAYER FOR TRANSPLANT Principal Investigator & Institution: Mckay, Brian S.; Ophthalmology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2003; Project Start 13-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): Age-related macular degeneration (AMD) is a disease that affects many in our aging population. The end result of this disease is blindness and there is no cure. Current treatments center on re-establishing contact between the neural sensory retina and its supporting tissue, the retinal pigment epithelium (RPE). There are two current surgical methods to accomplish this task, either macular translocation or RPE transplantation. Macular translocation involves detaching the retina, cutting it circumferentially, and mechanically rotating the retina such that the macula is placed onto a healthy bed of RPE. This is a very technical and difficult surgery that requires significant follow up and may not be appropriate for many patients. RPE transplantation, can in animal models of disease, rescue retinal degeneration suggesting that this may be a valuable treatment option. However, RPE grafts in AMD patients suffer a high rate of graft rejection, limiting the usefulness of this treatment. This study is focused on preparing cultures of RPE cells from adult humans that are candidates for transplantation. The proposal is based on the novel observation that coordinated cadherin adhesion causes differentiation of human RPE cells. This observation suggests that it may be possible to produce RPE monolayers in culture that function as the tissue in vivo, and may yield beneficial results for transplantation. Significantly, our data suggests that the appropriate monolayers of RPE can be produced from passaged RPE that have expanded and proliferated extensively. This new method opens the opportunity to harvest a small number of RPE from a patient, expand the cells to produce enough for transplantation, stimulate differentiation, then transplant the patient's own RPE cells back under the retina. This procedure would avoid the graft rejection problems encountered using fetal RPE cells, RPE cell lines, or cultured RPE from generic donor tissue. The goals of this pilot project are to determine whether the methods developed are broadly applicable to RPE cultures from a spectrum of donors at different ages, to determine whether the 'tissue-type' monolayers produced express the functional characteristics necessary for function after transplantation, and to determine whether the monolayers can be produced on transplantable substrates. The results from this project will significantly impact both the treatment of the disease and the basic studies that seek a cure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHOROIDAL CIRCULATION & AGE RELATED MACULAR DEGENERATION Principal Investigator & Institution: Grunwald, Juan E.; Professor; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104

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Timing: Fiscal Year 2001; Project Start 01-JAN-2001; Project End 31-DEC-2004 Summary: (Applicant's Description): Age-related macular degeneration (AMD) is the leading cause of blindness in people over the age of 65 in the United States. About 10 percent of the U.S. population will develop AMD and 1 percent may suffer from the more advanced, exudative form of the disease that leads to severe visual impairment. The basic mechanism involved in the development of this disease is not clearly understood. One of the most common manifestations of this disease, however, is the deposition of materials that are not adequately removed from the retinal pigment epithelium-Bruch's Membrane interface. Several recent reports and some preliminary data from our laboratory have suggested abnormalities of the choroidal circulation in AMD. These reports are of great interest because this circulation supplies all metabolites and removes all waste products from the outer retina. An abnormal choroidal circulation could have a role in the process that leads to the accumulation of these abnormal substances. In addition, a decreased choroidal vascular supply could also lead to ischemia and hypoxia of the outer retina and this could be associated with the development of choroidal neovascularization, a blinding complication of AMD. The main aim of this application is to use the state-of-the-art non-invasive technique of laser Doppler flowmetry to investigate whether choroidal blood flow and its regulation are abnormal in AMD, and whether a more abnormal choroidal circulation is associated with a higher risk of developing choroidal neovascularization and the more advanced and blinding stages of AMD. A better understanding of the mechanisms associated with the development of AMD could, in the long run, help us devise new treatment strategies for this devastating disease. In addition, the knowledge gained through this investigation could also help in the identification of patients at risk of developing choroidal neovascularization, thus enabling earlier treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CONFERENCE--RETINAL DEGENERATION Principal Investigator & Institution: Anderson, Robert E.; Professor; Ophthalmology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: (Applicant?s Abstract) The primary goal of the forthcoming X International Symposium on Retinal Degenerations, a satellite meeting of the XV International Congress of Eye Research, is to promote the exchange of current information and ideas amongst basic and clinical scientists in the interest of fostering new advances in our understanding of basic mechanisms and the development of therapeutic interventions in acquired and inherited retinal degenerations. Special effort has been made to introduce new investigators into the field and to include established investigators with clinical and basic science backgrounds. We have reached a point in the history of scientific endeavor at which there is common interest among basic and clinical scientists in understanding the fundamental mechanisms underlying retinal diseases. This meeting, which has been held biennially since 1984, has been responsible for fostering many of the collaborative research projects that have provided vital new information. As with previous meetings, the 2002 conference will feature a rich mixture of investigators, ranging from cell and developmental biologists to clinician-scientists from major research/clinical centers throughout the world. The 2002 meeting will be held in Antalya, Turkey on Sept. 29 Oct. 5, 2002 as a satellite meeting of the XV International Congress of Eye Research to be held in Jerusalem from Oct. 6 - 11. The meeting will have eight sessions of paper presentations and dedicated time for poster discussion. The program will be finalized 3-

14

Macular Degeneration

4 months before the meeting and will include the very latest information. Topics covered in previous meetings include new genes and loci, gene therapy, macular degeneration, animal models, medical therapies, mechanisms of cell death, transplantation, and retinal prostheses. A highly favorable aspect of the nine meetings held to date is the intimate environments that have provided for formal and informal discussions among established scientists with diverse backgrounds. This relaxed atmosphere has allowed clinicians and researchers from all parts of the to meet each other and learn of each other?s work. From the first meeting held in 1984, we have encouraged young persons to attend. Beginning in 2000, we supported the attendance of eleven students, postdoctoral fellows, and young scientists new to the field, who had the opportunity to meet and interact with established scientists. This is a key feature that distinguishes the International Symposium on Retinal Degenerations from other scientific meetings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DEVELOPMENT OF A NEW ANTIANGIOGENIC TUMOR BLOCKER SBD 1 Principal Investigator & Institution: Bojanowski, Krzysztof; Ceo/ Scientist; Sunny Biodiscovery, Inc. 675 Hegenberger Rd, 2Nd Fl Oakland, Ca 946011919 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-OCT-2003 Summary: Inhibition of tumor angiogenesis-the growth of new blood vessels towards the tumor mass-is a new and promising approach to anti-cancer therapy. The results of Phase I/II clinical trials completed so far with several angiogenesis inhibitors validate the concept of tumor angiogenesis as effective target for anti-cancer therapy. However, the same studies stress the need for novel, more potent angiogenesis inhibitors. We addressed this need by isolating the human urine a new protein (SBD.1), which specifically blocks the proliferation of capillary endothelial cells in vitro (ID50=15NG/ML), angiogenesis in chorioallentoic membrane assay, and two growth in vivo (Lewis Lung Carcinoma, T/C=0.04 at 20umum/kg/day), placing SBD.1 among the most potent known angiogenesis inhibitors. Sequencing of SBD/1 showed it is a novel protein and its mild proteolysis resulted in the generation of smaller peptides without losing the inhibitory activity. Here, we propose to a) clone and express SBD.1 in a recombinant system; b) isolate and sequence the activity SBD.1 fragments; c) test the purified SBD.1 on prostate, lung and breast carcinoma human xenografts in nude mice to further assess its anti-tumor activity This project will result in the cloning of a novel therapeutically-active protein, which may be an important endogenous regulator of angio- and tumorigenesis in humans. PROPOSED COMMERCIAL APPLICATIONS: The development of SBD.1 addresses a pressing need in the pharmaceutical industry for a new, better angiogenesis inhibitor. Currently targeting anti-cancer therapy, the use of SBD.1 might be later extended to the treatment of vascular pathologies, such as macular degeneration and certain cardiovascular diseases. Meanwhile, SBD.1 can also be commercialized as reagent for laboratory research on angiogenesis. Taken together, these applications represent a substantial potential market for SBD.1 Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DIABETES AND CARDIOVASCULAR DISEASE IN FILIPINA WOMEN Principal Investigator & Institution: Araneta, Maria R.; Family and Preventive Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093

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Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): This proposal is designed to assess the relationship of noninsulin dependent diabetes (NIDDM) and its covariates to macrovascular and microvascular disease in a previously unstudied ethnic cohort by: 1. Providing support to an "under-represented investigator" Maria Rosario G. Araneta, Ph.D., an epidemiologist of Filipina descent. The present proposal will enable Dr. Araneta the opporunity to gain research experience in diabetes epidemiology, through the mentorship of Dr. Elizabeth Barrett-Connor, and collect and analyze data on which to base a subsequent research grant application on diabetes research. 2. Continuation of the UCSD Filipina Womens Health Study, a cross-sectional study of Filipina women aged 40 and above in San Diego County, through: a) a follow-up telephone interview to determine changes in morbidity, mortality, and medication use since their initial clinical evaluation in 1995-1999, and b) record review validation of reported cardiovascular disease. 3. Conducting statistical analyses of newly obtained data and data from the clinical evaluation to explore the relationship between NIDDM and its covariates, and the metabolic syndrome and its components to macrovascular (cardiovascular and lower extremity arterial disease) and microvascular disease (microalbuminuria, nephropathy, diabetes retinopathy, visual impairment and macular degeneration) among Filipina women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DIRECTED GENE TRANSFER INTO RPE CELLS Principal Investigator & Institution: Chaum, Edward; Ophthalmology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2001; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: The retinal pigment epithelium (RPE) plays a critical role in maintaining the health and function of the neurosensory retina. Inherited and acquired RPE dysfunction is responsible for a number of important blinding diseases including certain forms of retinitis pigmentosa, retinal dystrophy and age-related macular degeneration. We believe that the greatest promise in the potential treatment of inherited and acquired retinal degeneration lies in the development and refinement of directed gene therapy to the host retinal pigment epithelium. Our working hypothesis is that directed liposomemediated gene transfer can transfect RPE cells in vivo with high efficiency and can deliver functional genes which are capable of sustained expression in host RPE. The conceptual basis for this hypothesis is that the intrinsic phagocytic function of the RPE makes this cell an ideal host recipient for liposome-mediated gene transfer. Liposomemediated gene transfer allows transfection of large molecular weight DNA s, potentially translatable genes capable of replacing the defective genes which result in retinal degeneration. Specific Aims and Methods 1: Develop and optimize an efficient liposome- mediated gene transfer protocol for mammalian retinal pigment epithelial cells in vitro: i) assess and optimize conditions of in vitro endocytosis of liposomes in human and rabbit RPE cells, ii) determine relative delivery efficiencies of different liposome preparations in humans and rabbit RPE cells, and iii) assess relative toxicity of different liposome preparations on cells in vitro. 2: Assess exogenous DNA uptake and expression frequencies in RPE cells by liposome-mediated gene transfer utilizing the reporter gene beta-galactosidase or the selective marker gene neomycin resistance: i) quantitate uptake of exogenous DNA sequences, ii) determine in vitro culture and transfection conditions which maximize DNA uptake in the human and rabbit RPE cell lines, iii) quantitate transcription and translation of exogenous DNA sequences. 3: Optimize this liposome-mediated gene transfer system for mammalian retinal pigment

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Macular Degeneration

epithelial cells in vivo: I) assess toxicity of liposome/DNA complexes in the living retina, ii) assess transfection efficiencies in the retinal pigment epithelium, iii) optimize conditions for gene transfer to RPE cells in vivo and assess duration of expression of transfected genes in the living retina. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DRUSEN CHARACTERIZATION

AND

AMD:

SUB-TYPE

ISOLATION

AND

Principal Investigator & Institution: Hollyfield, Joe G.; Director of Research; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 02-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The broad, long-term objective of this application is to define in molecular terms the linkage between the accumulation of soft drusen below the retinal pigment epithelium (RPE) in the macula and the increased risk of developing age-related macular degeneration (AMD). The presence of soft drusen in the macula is the hallmark risk factor for developing AMD. Surprisingly little is known of the composition or origin of drusen. To this end a novel method for drusen isolation has been developed that allows the collection of microgram quantities of drusen from donor eye tissue. At the time of isolation, different drusen sub-types can be identified and separated for use in studies that will characterize their molecular composition. The diagnostic utility of drusen in AMD can be likened to that of blood levels of cholesterol in atherosclerosis. The presence and abundance of drusen, like the level of cholesterol in the blood, indicates the degree to which a patient is at risk for developing the disease. Because of the relationship of drusen and AMD, understanding the composition of different drusen sub-types will provide important information on possible pathways that are causally involved in drusen development. Novel proteins or common modifications of proteins present in drusen, should provide insight as to potential drug targets of therapeutic agents to treat AMD. The current application is focused on exploiting this drusen isolation procedure to define the molecular composition, distribution and cellular origin of drusen sub-types in normal and AMD tissues. The three specific aims are: (1) To test the hypothesis that different sub-populations of drusen can be isolated from donor eye tissue. (hard vs. soft, foveal vs. peripheral, old vs. older, spherical vs. flat, amber vs. clear, opaque vs. granular, etc.). (2) To test the hypothesis that different structural features of drusen sub-populations reflect different molecular composition (light microscopy, histochemistry, electron microscopy, SDS/PAGE, Western blotting, mass spectrometry). (3) To test the hypothesis that some of the molecules present in drusen are novel and are not found in Bruch's membrane. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF ISOPROSTANES ON RETINAL TRANSMITTER RELEASE Principal Investigator & Institution: Opere, Catherine A.; Pharmacy Sciences; Creighton University 2500 California Plaza Omaha, Ne 68178 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Isoprostanes (IsoP's) are a series of prostaglandinlike compounds that are formed in abundance in vivo by a non-enzymatic, free radical catalyzed peroxidation of arachidonic acid independent of cyclooxygenase. In addition to providing a reliable measure of in vivo and in vitro oxidative stress, IsoP's can exert pharmacological effects in some tissues. A review of literature revealed that very few

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studies have addressed the effects of IsoP's on neurotransmitter release from central or peripheral tissues. Although IsoP's have been reported to modulate sympathetic neurotransmission from anterior uveal tissues, no studies have investigated the potential regulatory effects of these compounds on neurotransmission in the retina. In the present study, we will test the hypothesis that IsoP's can modulate glutamate, gamma-aminobutyric acid (GABA) and dopaminergic transmission in the retina both in vitro and in vivo. The overall objective of the present study is to examine the effect of different series of IsoP's (A1, E1, E2, F1, F2 and F3) on glutamate, GABA and dopamine release from retinae both in vitro and in vivo. Experiments in this project have, therefore, been designed to answer the following questions: (i) do different IsoP's alter the release and/or availability of glutamate, GABA and dopamine in vitro and in vivo? (ii) are the effects produced by IsoP's comparable to those of other arachidonic acid metabolites (prostaglandins and thromboxanes)? (iii) what is the role of presynaptic IsoP heteroreceptors in the effects caused by these compounds on glutamate, GABA and dopamine in vitro and in vivo? We anticipate that the results of the present study will improve our understanding of the basic mechanisms involved in the effects of IsoP's on retinal glutaminergic, GABAergic and dopaminergic transmission. Furthermore, these studies may reveal pharmacologically/toxicologically accessible sites for the action of IsoP's in the retina. We hope that observations made in this project will be applicable to diseases of the retina associated with the generation of free radicals and oxidative damage such as ischemia, glaucoma, diabetic retinopathy and age-related macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ELASTIC FIBER DEFECTS IN PSEUDOXANTHOMA ELASTICUM Principal Investigator & Institution: Boyd, Charles D.; Professor of Cell Biology & Program Dire; None; University of Hawaii at Manoa Honolulu, Hi 96822 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2003 Summary: The aim of this proposal is to understand the biological and pathogenetic basis of elastic fiber defects in a heritable disorder of cutaneous, vascular and ocular tissue, pseudoxanthoma elasticum (PXE). PXE is a heritable disease characterized by the accumulation of abnormal elastic fibers in several elastic tissues, particularly the skin, arteries and the elastic Bruch's membrane of the retina. The aberrant deposition of calcified elastic fibers in these tissues is responsible for the development of the clinical symptoms characteristic of PXE and these include inelastic skin lesions, retinal hemorrhage with partial loss of vision and vascular defects such as gastrointestinal bleeding and myocardial infarction. The pattern of inheritance of PXE is complex and both autosomal dominant and recessive forms of the disease have been reported. Over the last few years, several groups of investigators have attempted to identify the gene mutation(s) responsible for PXE but it has only been in the last two years that three separate laboratories, including our own, have located a major locus for this disease on the short arm of chromosome 16. We have now successfully identified a region at 16p13.1 of 820kb that contains 6 candidate genes, at least one of which will contain the mutations responsible for PXE. With this new information, we hope to identify the 'PXE gene', the mutations in this gene in a cohort of PXE patients and determine a possible function for the product of the PXE gene. These goals are focused on elucidating the biology of PXE and using this information to provide a better understanding of the role of elastic fibers in more common elastic tissue diseases, particularly those skin, vascular and eye disorders characterized by tissue calcification such as the many dystrophic

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Macular Degeneration

calcification disorders of skin, aneurysms, atherosclerosis and age-related macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENDOTHELIAL TRANSMIGRATION ACROSS THE RPE BARRIER Principal Investigator & Institution: Hartnett, Mary E.; Associate Professor of Ophthalmology; Ophthalmology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Choroidal neovascularization (CNV) is the primary cause of severe vision loss in age-related macular degeneration (AMD), but little is known about the complex mechanisms leading to CNV growth into the neurosensory retina. Human histopathology of occult CNV in AMD has shown that contact between the endothelial cells (EC) of the choriocapillaris and the retinal pigment epithelium (RPE) leads to compromise of the RPE barrier, which precedes the growth of CNV into the neurosensory retina. We will test the hypothesis that RPE-EC contact causes a functional change in the RPE monolayer that permits the transmigration of EC across the RPE. Specifically, we will determine whether 1) EC contact with RPE causes compromised RPE barrier function and structure; 2) EC contact with RPE causes a major change in the ratio of angiogenic stimulators to inhibitors (i.e., VEGF: PEDF) in the RPE; and 3) RPE-EC contact specifically activates cell-associated RPE VEGF isoforms that enable transmigration of EC across the RPE monolayer. Methods will include measurement of transepithelial electrical resistance (TER), cell counts, viability tests, and staining for ZO-1, n-cadherin, and actin in human cell co-cultures of RPE and EC to evaluate RPE barrier structure and function; ELISA, Western blot, and Northern blot to quantitate VEGF:PEDF ratios under various culture conditions; staining for actin and barrier proteins, TER, permeability, and RT-PCR to quantitate soluble and cellassociated VEGF isoforms; and fluorescent labeling of RPE and EC to follow transmigration of EC. Approximately 90% of the legal blindness that occurs in patients with AMD is the result of CNV that originates from the choriocapillaris and grows beyond the natural boundaries of Bruch's membrane and the outer blood-retinal barrier of the RPE into the neurosensory retina. Increased knowledge of the mechanisms that cause this destructive phenomenon may lead to future means to prevent CNV in the neurosensory retina, and thus, reduce vision loss in AMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EPIDEMIOLOGY OF AGE RELATED OCULAR DISEASE Principal Investigator & Institution: Klein, Ronald; Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 16-JUN-1987; Project End 31-MAY-2002 Summary: (Applicant's Abstract) This proposal describes a population-based cohort study aimed at determining the long-term (10-year) incidence and progression of the most common vision-threatening conditions of adult Americans, age-related cataract and maculopthy, and their risk factors. The population was 43-86 years of age at the census prior to the first survey in 1987-88. Standardized protocols for interviews, examinations, ocular photography, and grading have been employed during the baseline (n=4,926) and the 5-year follow-up (n=3,816) examinations. Refusal rates have been low. Because this cohort initially included a substantial number of middle-aged adults, the study provides a unique opportunity to follow the course of these eye

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conditions and document their natural history as this population enters the age of marked increase in disease incidence. The study in its initial prevalence survey and at the 5-year follow-up obtained information about cardiovascular disease, hypertension, diabetes and other medical conditions, cigarette smoking, nutritional supplements, light exposure, drug use history, and blood factors (e.g. glycosylated hemoglobin, total and HDL cholesterol). The 10-year follow-up is essential because the cohort is maturing and the number of cases of disease will be great enough to test many of the hypotheses that could not be precisely tested when the population was younger. In addition, at the 5year examination, additional questions were added regarding subjective assessment of visual ability and history of falls and fractures, while continuing to monitor other risk factors and ocular variables that were measured at baseline. We will examine the relationship of impaired vision from specific age-related eye conditions to self-reported visual function, falls, and fractures and nursing home placement. Frequencies of agerelated maculopathy differ between whites and ethnic minority groups. We will determine the relation of risk factors (cardiovascular disease, hypertension, diabetes, other characteristics as described above) for age-related maculopathy in nonHispanic whites, nonHispanic blacks and Mexican Americans participating in the National Health and Nutrition Examination Survey III (NHANES III) and whites and blacks participating in the Atherosclerosis Risk in Communities (ARIC) study. Existing graded fundus photographs will be used. Findings regarding cataract and age-related maculopathy will be of great public health importance in helping to predict the requirement for visual care and rehabilitative services as the population ages, and in directing further efforts at preventing these conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ETIOLOGIC DEGENERATION

STUDIES

OF

AGE-RELATED

MACULAR

Principal Investigator & Institution: Seddon, Johanna M.; Associate Professor; Massachusetts Eye and Ear Infirmary 243 Charles St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-MAR-1996; Project End 31-MAR-2007 Summary: (provided by applicant): We hypothesize that underlying susceptibility gene (s) are critical to the development of age-related macular degeneration (AMD) and that they most likely interact with environmental factors to trigger the development and progression of this disease. We propose a multi-pronged approach to the identification of susceptibility gene(s) for age-related macular degeneration (AMD). During the initial grant period we developed a large genetic AMD database including large families and multiplex families with affected sib-pairs, and have identified several areas of genetic linkage to pursue. During the next grant period, we propose a multipronged approach to build upon this database, with the goal of finding the gene or genes associated with AMD susceptibility. We will use family-based and population-based case-control association studies, combined with an expanded genome-wide sib-pair study for this project. Single nucleotide polymorphisms in high priority positional or functional AMD candidate loci will be genotyped for the association studies and linkage disequilibrium and transmission disequilibrium tests will be performed. Sib-pair linkage analysis using both quantitative and qualitative traits on the expanded genome-wide scan will be completed. We will collect family history and risk factor data and conduct studies examining these risk factors for AMD. These data will provide important information to analyze the influence of environmental factors as information about specific genetic factors involved in the disease is identified. This study should provide important new information about the etiology of AMD which is the leading cause of irreversible

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Macular Degeneration

blindness among elderly individuals worldwide, so that preventative or treatment measures can be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTIONAL ANALYSIS OF THE RETINAL REGULATORY PROTEIN RB Principal Investigator & Institution: Harbour, J W.; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-JAN-1998; Project End 31-DEC-2002 Summary: The candidate's long-term career goal is to combine his clinical interests in retinal diseases with his research interests in molecular biology. Washington University in general, and the sponsor's laboratory in particular, provides an exceptional setting for the candidate to pursue this goal. The sponsor's laboratory is a vigorous intellectual environment where many important contributions have been made in understanding the structure and function of the retinoblastoma protein (Rb) in health and disease. Further, the sponsor has an outstanding record of training successful clinician-scientists. The candidate's research will focus on the normal structure and function of Rb. While Rb was initially discovered through its role in the development of retinal tumors, it is now clear that Rb plays an important role in normal growth and differentiation of the retina. Understanding the normal function of Rb is likely to have significant implications not only for retinoblastoma, but also for macular and retinal degenerations, photoreceptor regeneration, and retinal transplantation. The candidate proposes a series of experiments to further elucidate the interaction between Rb and the E2F family of transcription factors. This interaction appears to be critical for cell cycle regulation and cellular differentiation. When Rb binds E2Fs, it blocks transcription from cell cycle genes that have E2F sites. In this proposal, the candidate will use a wide range of techniques, including transfection assays, and in vitro and in vivo binding studies to address the following specific aims: (1) determine regions in domains A and B of Rb that are responsible for transcriptional repression, (2) determine regions in domains A and B that mediate interdomain binding to form the active repressor motif, and (3) identify retinaspecific transcription factors that are inhibited by Rb. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: FUNCTIONS OF UBIQUITINYLATION IN THE MAMMALIAN RETINA Principal Investigator & Institution: Obin, Martin S.; None; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2001; Project Start 01-APR-1997; Project End 31-MAR-2004 Summary: (Adapted from applicant's abstract): Selective (nonlysosomal) proteolysis serves two vital functions in cells : (1) it controls steady-state levels of proteins whose concentrations and activities must be precisely regulated to maintain homeostasis and differentiation pathways; and (2) it protects cells from insults such as oxidative stress, viral infection and mutations by degrading potentially cytotoxic damaged or aberrant proteins. The importance of selective proteolysis to cell regulation and to stress and disease resistance is underscored by the fact that eukaryotic cells possess a highly conserved and exquisitely selective proteolytic pathway that recognizes and degrades both native regulatory proteins as well as aberrant proteins resulting from stress and disease. This pathway requires ubiquitin, a protein which is abundant in all cells; hence, the pathway is called the ubiquitin-dependent pathway (UDP). Studies from the

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applicant's laboratory indicate that the UDP functions in mammalian ROS and suggest that the visual transduction GTP-binding protein (G protein), transducin, is a UDP substrate. These observations suggest a novel mechanism by which photoreceptor proteins may be selectively regulated as well as the potential for modulation of the visual transduction cascade by the UDP. One long-term objective of the applicant's research program is to determine the function of the UDP in photoreceptors. In pursuit of this goal, the proposed research will (1) confirm the presence of the UDP protease in rat ROS using immunoelectron microscopy and (2) demonstrate UDP proteolytic function in cell-free preparations of gradient-purified bovine ROS (specific aim 1). The applicant will subsequently determine (3) if purified transducin is degraded by the UDP in ROS preparations and (4) the extent to which light-induced transducin dissociation alters its degradation by the ROS UDP (specific aim 2). In humans, protein damage in the normal retina resulting from (photo)oxidation is implicated in age-related macular degeneration (AMD), and expression of aberrant proteins in the diseased retina is causally associated with the pathogenesis of progressive retinal degenerations (retinitis pigmentosa). Thus, an additional long-term objective of the applicant's research is to determine how damaged and mutant proteins are removed from cells in the intact and diseased retina. In pursuit of this goal, experiments described under specific aim 3 will (1) use immunohistochemistry and western blotting to confirm a previous report of increased UDP-modified protein in retinas of Long-Evans rats exposed to photic stress (prolonged bright light) and to determine where within retinal cells these increases are manifest; (2) determine if increased protein flux through the UDP in response to photic stress reflects increased UDP efficacy and/or increased substrate availability; and (3) initiate studies designed to elucidate the molecular and biochemical mechanisms by which UDP efficacy is altered in response to photic stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION ANALYSIS IN MICROCAPTURED RETINAL CELLS Principal Investigator & Institution: Adler, Ruben; Arnall Patz Distinguished Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Retinal degenerative diseases are a major cause of visual disability and blindness worldwide. Age-related macular degeneration (AMD), for example, is the leading cause of blindness in the elderly in the Western world. Current treatments do little to alter the inexorable loss of vision due to retinal degenerations. Several studies have shown that intraocular injection of factors such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor-2 (FGF2), slows photoreceptor cell death caused by specific mutations or exposure to constant light. However, the clinical usefulness of these findings may be limited, because rescue effects are partial and transient, and some factors appear to have unwanted side effects. Elucidation of the mechanism by which survival factors delay retinal degenerations appears necessary in order to maximize benefits and minimize side effects. Recent studies from our laboratories have suggested that CNTF, BDNF and FGF2 do not act directly on photoreceptors; rather, they appear to act indirectly through other cells, most likely M ller cells. Based on these observations, we propose to investigate the molecular changes triggered by neurotrophic factors in M ller cells. The studies involve the combined use of two complementary and demanding state-of-the-art techniques: the generation of cDNA from individual cells, and their analysis using custom designed retinal cDNA microarrays. We will then

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Macular Degeneration

establish which of these changes are important for photoreceptor survival. The potential impact of the identification of these molecules is clear, since they could offer new avenues for the treatment of these devastating diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENE EXPRESSION PROFILES OF RETINAL DEGENERATION Principal Investigator & Institution: Cepko, Constance L.; Professor; Genetics; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Many diseases that ultimately lead to blindness are caused by the degeneration of photoreceptor (PR) cells. Cones typically die after rods, with kinetics somewhat dependent upon the particular disease. Rod loss followed by cone loss is also seen in cases where a genetic etiology has not been established, as in some forms of macular degeneration. While humans are able to function quite well without rods, the loss of cone-mediated vision is devastating. The reason(s) that cones die in these cases is unknown. However, since cone loss can be initiated by events that are not intrinsic to cones, these events must include some type of cell-cell interaction, perhaps including the action of a secreted molecule(s). Such a process may be susceptible to interruption through the application of a pharmacological or a cell based therapy. In addition to progressive diseases such as retinitis pigmentosa, there is a mouse model, the cyclin D1 knock-out (KO) mouse, in which degeneration is arrested. The cause of PR death, as well the cause of the arrest, are unknown. This model may provide some insight into how degeneration can be arrested in progressive diseases. We are seeking to use retinal microarrays to define the gene expression changes that accompany PR death in mice, with an emphasis on the events that lead to cone death. In addition, we will characterize the gene expression changes that accompany the arrest of PR degeneration in the cyclin D1 mutant. We further plan to characterize the expression patterns of such genes in normal and pathological tissue. Finally, we will explore the function of some of these genes using genetic approaches in mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETIC DEGENERATION

MODEL

OF

RETINAL

PIGMENT

EPITHELIUM

Principal Investigator & Institution: Vollrath, Douglas E.; Associate Professor; Genetics; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Animal genetic models have been essential to the understanding and treatment of human retinal degenerative disease. The importance of the retinal pigment epithelium (RPE) to photoreceptor function is widely recognized. Primary degeneration of RPE cells is thought to be central to the etiology of several significant human retinal disorders including age-related macular degeneration (AMD) and pigmentary retinopathies associated with mitochondrial dysfunction, yet no animal genetic model of a primary RPE cell degeneration exists. This proposal describes a strategy to create such a model using mouse genetics. A mouse strain will be generated in which RPE cells gradually and postnatally degenerate and die due to RPE specific loss of mitochondrial function. RPE cell degeneration should induce secondary photoreceptor cell degeneration and choroidal atrophy. A detailed structural and functional analysis of the effects of RPE cell loss on the RPE and adjacent tissues will be performed at various ages. At an appropriate stage in the degeneration, the model will

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be perturbed by modulating light exposure. A model of primary RPE cell degeneration will be useful for understanding the interdependence of RPE and photoreceptor cells and of the RPE and choroid, for understanding pathogenic processes secondary to RPE cell death, and for investigating potential therapies in a setting in which RPE cell function is progressively compromised. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC STUDIES OF OCULAR ANGIOGENESIS Principal Investigator & Institution: D'amato, Robert J.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Angiogenesis, the formation of new blood vessels, is a tightly regulated function determined by the local balance of endogenous angiogenesis stimulators versus inhibitors. The central hypothesis for this proposal is that the angiogenic balance varies between individuals and that this variation is in large part genetically determined. Indeed, epidemiological data suggests that different racial populations have varied susceptibility to ocular neovascularization. We have surveyed inbred mouse strains to see if mice have a range of angiogenic diversity that models that of humans. Surprisingly, we found a large range of angiogenic responses to pellets of basic fibroblast growth factor (bFGF) implanted in the corneas of different strains. The difference between the lowest response and the highest response was 1200 percent. To date, the most sensitive strain is an albino mouse known as 129. In this strain, corneal bFGF pellets induce very aggressive corneal and iris neovascularization as compared to C57 black mice which have moderate corneal angiogenesis and no iris neovascularization. Interestingly, tyrosinase positive substrains of 129 mice (which are pigmented), retain the overly aggressive corneal neovascular response but do not have iris neovascularization. To evaluate the aggressive corneal angiogenic response of the 129 mice we propose to breed them with other inbred strains with lower responses. We will then characterize the angiogenic phenotype of the offspring of the crosses and will use genetic mapping to identify the chromosomal locus that segregates with this phenotype. If there are candidate genes in the region, these will be screened for alterations in DNA sequence. The goal of this proposal is to characterize the angiogenic phenotypes of different murine inbred strains and to identify the genetic contributions to these phenotypes. Identifying the genes controlling ocular angiogenesis in mice will help find similar genes in humans, the characterization of which may suggest new therapies for pathologic neovascularization seen in neovascular glaucoma and macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENETICS OF AGE RELATED MACULAR DEGENERATION Principal Investigator & Institution: Klein, Michael L.; Director; Ophthalmology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: Age-related macular degeneration (AMD) is recognized as the leading cause of blindness in the United States. It affects nearly 1.5 million older Americans and causes loss of vision in more than 7 percent of individuals over 75 years of age. Currently, there are no established means of preventing AMD. The only proven effective treatment, laser photocoagulation, is successful in only a small proportion of cases. While the etiology of AMD is unknown, there is considerable evidence implicating a strong genetic

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Macular Degeneration

component for the disease. Advances in genomic screening and analysis methodologies make a direct genetic approach to the etiology, pathophysiology, and ultimate therapy of AMD viable. Recent successes with other complex traits, which share genetic and epidemiological similarities with AMD, support the idea that identification of genetic loci responsible for AMD is an achievable goal. The long-term objectives of this project are to identify genes responsible for AMD, develop diagnostic tools to identify patients at risk of developing the disease, and to understand its molecular pathophysiology. This understanding will allow the development of preventive measures and improved methods of treatment. The immediate goal of this research proposal is to map genetic loci cosegregating with AMD in a number of affected families. We will employ both parametric and several nonparametric linkage analysis methods. To achieve these goals, we propose to: 1) Continue to collect additional kindreds containing multiple affected living members; 2) Complete genome-wide screening of AMD families, beginning with a set of candidate loci; 3) Fine-map loci suggestive of linkage and conduct detailed multi- point parametric and nonparametric linkage analysis; and 4) Refine identified loci and begin studies to identify the specific genetic defects responsible for AMD in these families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETICS OF AGE RELATED MACULOPATHY Principal Investigator & Institution: Gorin, Michael B.; Associate Professor; Ophthalmology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-SEP-1993; Project End 31-JUL-2002 Summary: Age Related Maculopathy (ARM) is the leading cause of vision loss in the elderly population in the United States and Western world and is a major public health issue. Epidemiologic studies have indicated that heredity is a significant risk factor and family studies have further substantiated that ARM can be inherited as a dominant disease with late age of onset and variable expressivity. ARM is not well suited for traditional genetic investigations due to difficulties of clinical ascertainment and the small pedigrees because of its late onset. However, nonparametric linkage methods including Affected Pedigree Member method and simIBD provide a means of determining genetic loci that contribute to ARM susceptibility using small and intermediate-sized families. In our previous project we ascertained over 200 ARM families and are in the process of completing a candidate locus screening as well as a genome-wide scan of the first 120 families with 161 autosomal markers (average spacing of 20 cM). We have established a classification system that allows us to evaluate a stringently defined ARM population as well as larger sets of patients with less severe and/or ambiguous phenotypes. Several markers used in the initial candidate gene screening and chromosome-wide panels have provided results that suggest linkage with ARM. These will be investigated during the next grant period. We are proposing to expand our recruitment of ARM families to 1000 families and pursue a combination of genome-wide scans (200 and 350 families) with 10 cM resolution and focused genotyping based upon the tentative positively linked loci determined during the first grant period. The large number of families is necessary to confirm and further resolve potential ARM loci so that we can undertake candidate gene screening of our ARM population. The families that are not used in the genome-wide scans will be used for the focused genotyping effort, in the candidate gene screening program, and for disequilibrium linkage studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GLIAL-NEURONAL INTERACTIONS IN THE RETINA Principal Investigator & Institution: Newman, Eric A.; Professor; Neuroscience; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2001; Project Start 01-JUL-1990; Project End 31-MAR-2005 Summary: (Verbatim from applicant's abstract): The long-term objective of this project is to determine the functions of glial cells (Muller cells and astrocytes) in the mammalian retina. It is widely recognized that glial cells have important support functions in the retina, including uptake of neurotransmitters and regulation of extracellular potassium and pH. The role of glial cells in direct modulation of neuronal activity is not yet understood, however. In the preceding project period, we demonstrated that intercellular Ca2+ waves can be propagated through glial cells in the rat retina and that these glial Ca2+ waves modulate spike activity in neighboring neurons. In the proposed project period, we will extend our studies of glial modulation of neuronal activity and explore additional aspects of glial Ca2+ signaling with the goal of determining the significance of these interactions in vivo. The specific aims for the project period are: (1) to identify natural stimuli that elicit Ca2+ signals in retinal glial cells; the hypotheses to be tested are that: (a) chemicals released under normal or pathological conditions evoke glial Ca2+ increases, and (b) light stimulation evokes glial Ca2+ increases; (2) to test the hypothesis that spontaneous Ca2+ oscillations in glial cells modulate the activity of neighboring neurons, using regression analysis to correlate neuronal spike activity and membrane potential with Ca2+ levels in adjacent glial cells displaying spontaneous Ca2+ oscillations; (3) to characterize mechanisms of glial cell modulation of neuronal activity; the hypotheses to be tested are that: (a) excitatory neuronal modulation is mediated by release of glutamate from glial cells onto neurons, and (b) inhibitory modulation is mediated indirectly by glial activation of inhibitory amacrine cells; (4) to elucidate the mechanism by which Ca2+ waves are propagated in retinal glial cells; the hypothesis to be tested is that wave propagation is mediated by the release of ATP, which functions as an extracellular messenger; and (5) to characterize physiological changes in retinal glial cells elicited by propagation of Ca2+ waves; the hypotheses to be tested are that: (a) Ca2+ increases modulate inward rectifier potassium and Ca2+dependent potassium conductances, and (b) Ca2+ increases generate intracellular pH variations in retinal glial cells. Glial cells have been implicated in many types of retinal pathology, including diabetic retinopathy, glaucoma, and macular degeneration. Knowledge of the basic physiological properties of retinal glial cells and their interactions with retinal neurons will add to our understanding of how these cells contribute to retinal pathology. The research outlined in this application will provide significant progress towards this goal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HIGHER ORDER VISUAL PERCEPTION: LOW VISION IN ELDERLY Principal Investigator & Institution: Odom, James V.; Medicine; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Low vision is a major health problem, especially among the elderly; reduced vision impairs their ability to navigate in their environment, impairs their ability to perform activities of daily living independently, and places them at greater risk for accidents and death. Relatively little research has been directed to understanding the visual control of mobility and daily behavior in older Americans with reduced vision. Almost none of the research that has been performed has examined

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Macular Degeneration

higher order perceptual functions in the performance of tasks of daily living including mobility. Our long-range objective is to examine the impact of reduced vision on higher order perceptual abilities and the relationship of differences in higher order perception on the performance of simulated and real tasks of everyday living. In order to accomplish this long-range goal we have brought together a team of vision researchers, clinicians, and computer scientists. For the purposes of this small, pilot study grant application, our aims are more specific and restricted. One set of higher order variables that have been identified in the literature as particularly important in mobility are those related to the detection of optic flow and its components. However, we have been unable to find research related to low vision patients' abilities use optic flow for detecting heading or navigating in their environment. Our specific aim for this grant is to conduct a series of six experiments to provide data on the ability of patients with low vision to detect optic flow information. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HIGH-RESOLUTION IMAGING OF OCULAR MELANOMA AND RETINA Principal Investigator & Institution: Bartsch, Dirk-Uwe G.; Associate Professor; Ophthalmology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: (Applicant's Description): High-resolution imaging allows improved understanding of retinal disease and pathological conditions, particularly in prognosis of malignant choroidal melanoma, age-related macular degeneration, diabetic retinopathy, ocular complications of AIDS and glaucoma. The eye can only be regarded as a diffraction-limited optical system up to a pupil diameter of 3 mm. Standard retinal imaging technology uses a 3 mm imaging aperture to avoid the higher order aberrations of the outer cornea. However, if these higher order aberrations can be compensated, diffraction-limited imaging at 7 or 8 mm pupil diameter can be achieved. The numerical aperture of the diffraction-limited eye at 7 or 8 mm pupil will allow to visualize retinal detail that was previously not achievable in ophthalmology. To achieve this goal we plan to develop a wavefront sensor that will allow us to measure the existing aberrations of the measured eye. We will test it in an eye model, in animal eyes and in human eyes. The wavefront sensor will be attached to a fundus camera and scanning laser ophthalmoscopes. The second aim is to use an adaptive wavefront compensator to correct the aberrations in a feed-back loop setup. We will test the complete system of wavefront sensor and wavefront compensator in an eye model, in animal eyes and in human eyes. The wavefront compensator will be attached to a fundus camera and scanning laser ophthalmoscopes. The third aim is to used digital image processing to correct for the portion of the residual aberrations that could not be compensated with the adaptive wavefront compensator due to mechanical considerations. Our group has previous developed a wavefront sensor and wavefront compensator based on a micromachined membrane deformable mirror. Due to the limited number of electrodes, slow speed of our computer system and the mechanical stiffness of the membrane we were not able to completely correct all measured aberrations. Our preliminary work shows that the system is capable of allowing wavefront correction. In this study we plan to improve the acquisition speed of our wavefront sensor and wavefront compensator to allow rapid wavefront compensation. Our preliminary results have shown that even the best aberration compensation still suffers from residual wave aberrations. Since we can

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measure and characterize these aberrations, we can develop digital inverse filter based on our experience in image reconstruction to correct the acquired images. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EPITHELIUM

HOMEOSTATIC

ABILITY

OF

THE

RETINAL

PIGMENT

Principal Investigator & Institution: Miller, Sheldon S.; Scientific Director; Optometry; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2001; Project Start 01-FEB-1978; Project End 31-AUG-2005 Summary: (provided by applicant): The retinal pigment epithelium (RPE) lies in the back of the eye between the neural retina and its choroidal blood supply. This layer of epithelial cells serves to protect the health and integrity of the outer retina. In the choroid, abnormal blood vessel growth or choroidal neovascularization (CNV) occurs in diseases such as age related macular degeneration (AMD) - the major cause of blindness for people over the age of 60. Vascular endothelial growth factor (VEGF) and other proor anti-angiogenic factors are constitutively secreted by the RPE into the extracellular space on both sides of the epithelium. The effects of these molecules on RPE physiology are not known. Evidence from human pathologic specimens and from rodent models suggests that increased VEGF production by the RPE is the source of CNV. Research in this area is severely hampered by the lack of a small animal model in which VEGF secretion by the RPE induces CNV. In preliminary experiments, we have used gene transfer techniques to develop a rat model for stimulating blood vessel growth in the back of the eye. This model will be used to test the hypothesis that secretion of VEGF by RPE is critically important in generating choroidal neovascularization (CNV). Gene transfer techniques will be also used to inhibit or reduce this VEGF-induced abnormal blood vessel growth. These experiments should provide a deeper understanding of CNV and the basis for a potential therapy for diseases like AMD. Normally, there is a very close anatomical relationship between the RPE and the retina. Separation of these two tissues occurs in a whole host of pathologies that lead to the abnormal accumulation of fluid in the extracellular or subretinal space. This separation or retinal detachment can lead to a loss of vision. One of our goals is to develop a rat model of retinal detachment. This model will allow us evaluate putatively therapeutic molecules that work directly on the RPE to remove fluid from the subretinal space. This removal will restore the normal anatomical relationship between RPE and retina and should improve vision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERSPECTRAL MICROSCOPE FOR DRUSEN PHENOTYPING Principal Investigator & Institution: Truitt, Paul W.; Kestrel Corporation 3815 Osuna Ne Albuquerque, Nm 87109 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2004 Summary: (provided by applicant): The demonstration of a Fourier-transform hyperspectral microscope for high resolution spectral ex vivo characterization of human retinal tissue is the aim of this project. The spectral reflectance and intrinsic fluorescence nature of normal and pathological retinal tissue must be established without the interfering effects of the intervening ocular media. This motivates the immediate goal of integrating the Fourier-transform imaging spectrometer (FTIS) to a microscope. A hyperspectral microscope may be used in many areas of biological and medical research; tissue classification (normal vs. pathological) and characterization, detection of

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Macular Degeneration

bacteria, gene identification, chromatin distribution, drug safety and efficacy, molecular imaging, and countless other applications. The Fourier-transform technology provides for a large number of highly resolved spectral bands simultaneously spatial at each pixel in the scene. Since fluorescence intensities are several orders of magnitude less than the reflectance signal, it is necessary to use a spectrometer with the highest possible sensitivity and wavelength selectivity. The FTIS has the advantage over traditional dispersive-based spectrometers in that entrance aperture and spectral resolution are decoupled. Thus, the slit can be increased to allow more light into the system without reducing spectral resolution. Further, because the FTIS is a constant wave number device, it offers improved spectral resolution in the visible to short wave infrared bands for a given detector size over conventional dispersive spectral imagers. Finally, the spatially modulated device collects all spectral data at once, avoiding any issues with spectral registration that otherwise occur. The six-month Phase I project will demonstrate the sensitivity of the hyper-spectral imaging methodology for spectrally phenotyping drusen in age-related macular degeneration (ARMD) eyes. Our approach builds on Kestrel's existing hyperspectral instruments and software, developed through Department of Defense. High spectral (2-4 nm) and spatial resolution images will be collected of histological specimens from two normal donor eyes and two eyes with clinical evidence or pre-mortem diagnosis of ARMD. The integrated system will be calibrated and tested. Illumination requirements for recording fluorescence will be established. A detailed, multi-source data set will be produced consisting of measurements of reflectance and transmission spectra, and intrinsic fluorescence spectra. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: IMMUNE RESPONSES IN MACULAR DEGENERATION Principal Investigator & Institution: Cousins, Scott W.; Professor; Ophthalmology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: (Applicant's Description): Age-related macular degeneration (ARMD) is a progressive disorder of the retina occurring in people older than age 50 associated with vision loss coupled with a spectrum of specific clinical, physiological and histopathological features. The pathogenic mechanisms for these specific changes are unknown, but circumstantial evidence suggests a role for a macrophage-mediated component in ARMD. We propose the general hypothesis that choroidal macrophages observed in ARMD are blood-derived monocytes recruited to the choriocapillaris to scavenge debris and deposits trapped in Bruch's membrane. In this project, we propose two specific aims to explore macrophage activation under conditions relevant to ARMD. In aim 1, we will use freshly isolated blood monocytes from normal subjects or ARMD patients, to establish the existence of high and low activity monocytes and to determine if high activity is a prognostic marker for ARMD progression. In aim 2, using a mouse model for age-related subRPE extracellular deposit formation recently developed in our laboratory, we will induce high activity monocytes in mice and establish that these macrophages will increase the severity of RPE degeneration or rate of progression of deposit formation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INDUCED DEGENERATION

APOPTOSIS

IN

AGE

RELATED

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MACULAR

Principal Investigator & Institution: Ferguson, Thomas A.; Associate Professor; Ophthalmology and Visual Sci; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2003 Summary: (Applicant's Description) Neovascularization is the major cause of vision loss in patients with age- related macular degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity. AMD is the leading cause of blindness in the Western world in individuals over 60 years of age. Since a large proportion of the population is living well beyond this age, this is a significant threat to the quality of life in elderly people. In patients with AMD new vessel growth (angiogenesis) beneath the retina from the underlying choroid (choroidal neovascularization or CNV) is the major or cause of severe visual loss in these patients. We recently examined the role of apoptosis in controlling new vessel growth in the eye by examining the function of two molecules, Fas (CD95) and FasL (CD95L). Our studies revealed that FasL plays a significant role in controlling CNV, where FasL+ retinal pigment epithelial cells (RPE) prohibit the growth and development of new Fas+ subretinal vessels that damage vision. Studies described in this proposal are designed to thoroughly understand the role of Fas/FasL and apoptosis in the pathogenesis of AMD. We propose 5 aims. Aim 1 we will more completely evaluate the role of Fas/FasL in CNV in a mouse model using normal, Fas, and FasL defective mice. In Aim 2 we will study cell endothelial cells derived from the choroid and compare these to endothelial cells derived from other areas. We will examnine cell death, proliferation, and differentiation using in vitro models and characterize the role of the Fas antigen in these processes. Aim 3 will contains experiments to explore the function of FasL on RPE cells and determine how growth factors and MMP inhibitors can affect FasL function in these cells that are crucial in controlling CNV. Aim 4 will explore potential treatment modalities in CNV applying the knowledge we have gained concerning the regulation of FasL expression to the animal model. Finally, studies in Aim 5 will evaluate clinical specimens from patients AMD for Fas/FasL expression. Our studies should provide important insights into one of the leading causes of blindness in the western world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INHIBITION OF CNV USING A TRANSGENIC PEDF MODEL Principal Investigator & Institution: Duh, Elia J.; Professor; Ophthalmology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in the United States. Choroidal neovascularization (CNV) is largely responsible for severe vision loss from AMD. As new and promising treatments emerge for the treatment of choroidal neovascularization, in vivo approaches will be needed not only to evaluate efficacy, but also to address issues important for clinical trials (e.g., dosing, toxicity). We thereby propose to use an inducible transgenic mouse model as an innovative approach to the study of inhibition of CNV. Specifically, we propose to study the effects of pigment epithelium-derived factor (PEDF), which has emerged as a potent inhibitor of angiogenesis, with dramatic inhibitory effects on corneal, retinal, and choroidal neovascularization. Our long-term oal is to develop PEDF as a ther~eutic modality for

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Macular Degeneration

the prevention as well as treatment of choroidal neovascularization. We hyaothesize that PEDF can cause regression of existing choroidal neovascularization, in addition to inhibiting CNV formation. Accordingly, we propose the following Specific Aims: (1) Develop a transgenic PEDF mouse model with retina-specific, inducible expression of PEDF. Aim 1 will include the characterization of spatial, temporal, and quantitative expression of induced PEDF in the mouse model. (2) Define the potential of PEDF as a therapeutic agent for choroidal neovascularization using the laser-induced CNV model. Aim 2 will determine if transgenic PEDF expression can prevent choroidal neovascularization as well as cause regression of existing CNV. In addition, Aim 2 will address the PEDF dosage requirements required for prevention of CNV, as well as the duration of PEDF presence necessary for prevention. Finally, Aim 2 will determine if transgenic PEDF expression causes choroidal endothelial cell apoptosis in vivo. In our studies, we will adapt the tetracycline-inducible gene expression system to induce photoreceptor-specific expression of PEDF. We will study the effects of transgenic PEDF expression in mice on laser-induced choroidal neovascularization. It is anticipated that our proposal will provide a strong foundation for further studies regarding the mechanism of PEDF action. In addition, our studies will provide a new experimental approach for the study of candidate inhibitors of CNV, providing important data regarding efficacy, therapeutic dose, frequency of administration, and toxicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INVESTIGATIONS OF HUMAN CONE DIRECTIONALITY Principal Investigator & Institution: Burns, Stephen A.; Senior Scientist; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-NOV-1987; Project End 31-AUG-2006 Summary: (provided by applicant): The eye is a highly specialized optical system. Its proper function requires tradeoffs between image quality at a single wavelength and the need to operate over a wide range of conditions., Retinal image quality is determined by both the refractive elements of the eye (cornea and lens) and the cone photoreceptors. The cone photoreceptors play a critical role, since they preferentially capture light from a particular location in properties of the pupil, and because they discretely sample the retinal image. The interaction of cones and the refractive properties of the eye is not well understood, and is highly variable across individuals. Understanding of this interaction has high clinical relevance, since over 1,000,000 patients a year are undergoing some form of refractive surgery. Refractive surgery does not yet take into account the large intra-subject variations. If future plans for enhanced refractive strategies are to improve vision then they must be designed with an understanding of the tradeoffs and optimizations involved in image formation. This proposal will make both basic measurements of all aspects of image formation, and ask questions as to whether the aberrations of the eye arise from random errors, or are actually in some sense beneficial, providing increased uniformity of image quality with changes in the spectral content of the retinal image. We will measure the optical quality of the eye over the visible spectrum using modern wavefront sensing techniques. Using modern optical techniques we will obtain measurements of cone directional sensitivity and cone packing density. We will validate new optical techniques using psychophysical measurements. We will combine information on the wave aberrations of the eye with the measurements of directional selectivity and packing density of the cone photoreceptors to obtain individualized estimate of retinal image quality for both monochromatic and polychromatic light. Retinal image quality will be examined as a function of age and refractive error. We will use these data to test whether the incorporation of cone

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information into the estimates of retinal image quality generates a better description of patient visual performance. Finally, we will test whether the cones can actively respond to changes in the eye by re-orienting. Our long-term goal is to understand the factors involved in the initial stages of image formation in the human eye, including the contributions of the cornea, lens, and cone photoreceptors, as well as their interactions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ISOPRENOID METABOLISM IN THE RETINA Principal Investigator & Institution: Fliesler, Steven J.; Professor; Ophthalmology; St. Louis University St. Louis, Mo 63110 Timing: Fiscal Year 2001; Project Start 01-MAR-1988; Project End 31-MAR-2005 Summary: (provided by applicant): The long-range goal of this project is to determine the biological roles of cholesterol (CHOL) and related molecules in the retina in both normal and pathological states. Oxygenated derivatives of CHOL and other sterols occur naturally in cells and tissues, being formed both by autoxidation as well as enzymatically. Such "oxysterols" regulate normal cellular physiology, but also are potent cytotoxins that have been implicated in diseases such as atherosclerosis, diabetes, and cancer. The involvement of oxysterols in retinal diseases is unknown and has yet to be investigated. However, given the association between hypercholesterolemia and atherosclerosis as risk factors in prevalent retinal diseases such as age-related macular degeneration (AMD), research in this area seems warranted. Herein, we evaluate the formation and biological activity of oxysterols in the retina of normal rats in comparison with those that have been treated with a drug (AY9944) that causes accumulation of 7dehydrocholesterol (7DHC) in the retina and other tissues. AY9944-treated rats are an animal model for the Smith-Lemli-Opitz syndrome (SLOS), a common, autosomal recessive disease with associated ophthalmic defects, including retinal dysfunction. New results presented herein show that AY9944-treated rats develop retinal dysfunction prior to obvious histological damage, yet when exposed to intense green light for only 24 h, a massive, rapid retinal degeneration ensues that is much more severe and extensive than occurs in normal rats under the same conditions. We will examine the time course of retinal degeneration in AY9944-treated rats relative to controls, in both normal, dim cyclic lighting and with the "light damage" paradigm, correlating retinal structure and function with the formation, amounts, and types of oxysterols in the retina. We will compare the effects of intravitreally-injected oxysterols on the structure and function of the retina in normal rats, with and without pretreatment with dimethylthiourea (DMTU), a potent antioxidant. We also will evaluate the ability of DMTU pretreatment to reduce or prevent both oxysterol formation and the retinal damage observed in AY9944-treated and normal rats following exposure to intense green light. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MACULAR DEGENERATION: GENETICS OF 4 DISTRINCT PHENOTYPES Principal Investigator & Institution: Ayyagari, Radha; Ophthalmology and Visual Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 02-JUL-2001; Project End 31-MAY-2006 Summary: The focus of this proposal is to study the biological basis of macular degeneration as will be seen through four large independent pedigrees with distinct

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Macular Degeneration

forms of macular degeneration segregating in Mendelian fashion. We are in the process of positional cloning and candidate gene analysis of these pedigrees, with current emphasis on early onset atrophic macular degeneration. Currently no treatment is available for these debilitating diseases. Cloning of these genes will provide an opportunity to look at the process of degeneration of macula from four biological genetic perspectives. The four forms of macular degeneration we are studying are: (1). Early onset autosomal dominant atrophic macular degeneration (adMD), (2). X-linked cone-rod dystrophy (COD1), (3). Late onset atrophic macular degeneration (adMD) and (4). Hemorrhagic macular atrophy. We mapped the disease locus for early onset adMD to a 4.9 cM interval on chromosome 6q (6q-adMD) and for COD1 to about 1 cM at Xpll. We have excluded most of the known macular degeneration loci for late onset adMD and hemorrhagic macular degeneration, and a genome wide scan to localize the disease genes is in progress. We have constructed physical and transcript maps of the 6q-adMD interval. Characterization of genes corresponding to candidate ESTs in the critical region is currently in progress. We will work toward positional cloning by: (a) localizing the disease gene to a small interval by ascertaining additional members of the pedigrees and analyzing new markers, (b) Characterizing candidate genes, and (c) Screening candidate genes for mutations. Once the gene(s) for above macular degeneration(s) (MD) is cloned, we will study the possible association between the macular degeneration gene and other phenotypic forms of macular diseases including AMD. Because we can not work on all four pedigrees simultaneously, some of the work is planned for sequential analysis. This study will result in identification of gene mutations causing selective degeneration of macula. These genes will help in understanding the mechanism underlying the variable age of onset and variable rate of progression of the above degenerations and will assist in developing effective treatments either to slow the rate of progression or to delay the age of onset of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM NEOVASCULARIZATION

OF

MUTANT

TIMP-3

INDUCED

Principal Investigator & Institution: Tolentino, Michael J.; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Applicant's Abstract) The main objective of this proposal is to provide Dr. Tolentino a mechanism for rigorous training both technically and conceptually in gene therapy and molecular biology. Dr. Tolentino's long term goal is to become an independent investigator focusing on understanding the molecular mechanisms and developing treatments for pathologic ocular neovascularization seen in blinding conditions such as macular degeneration and diabetic retinopathy. The training plan proposed is essential for Dr. Tolentino to successfully pursue these long-term goals. The broad long-term research objective of this grant proposal is to understand the biochemical mechanisms that lead to choroidal neovascularization (CNV). The development of CNV in age related macular degeneration (AMD) is the leading cause of blindness in the United States. Patients with Sorsby's fundus dystrophy, an autosomal dominant form of macular degeneration, have similar clinical findings to AMD including CNV. These patients have been found to have a mutation in the tissue inhibitor of metalloproteinase-3 (TIMP-3) gene. The specific aims of this study are: Specific aim 1: To test the hypothesis that CNV induced by mutant TIMP-3 (mTIMP-3) is caused by loss of functionality or direct stimulation of angiogenesis by mTIMP-3. To accomplish this aim, mTIMP-3 transfected endothelial cell will be assayed for their

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ability to proliferate, form tubes and migrate to angiogenic stimuli in vitro. Sub retinal injections into normal and transgenic mice of adenovirus expressing mTIMP-3 will be performed to determine mTIMP-3's ability to cause sub retinal neovascularization in vivo. Specific aim 2: To test the hypothesis that upregulation of vascular endothelial growth factor (VEGF) and/or down regulation of pigment epithelial derived growth factor (PEDF) is involved in mTlW-3 induced CNV. Both mTIMP-3 transfected retinal pigment epithelial (RPE) cells and a transgenic mouse model with a human TIMP-3 mutation that develops CNV will be assayed for protein and mRNA upregulation using ELISA, northern blot, immunohistochemical and in situ hybridization techniques. Specific aim 3: To develop and test gene vectors expressing inhibitors of angiogenesis (angiostatin, endostatin, PEDF) and test their ability to inhibit subretinal neovascularization in the mutant transgenic mouse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF ORGANELLE DEGRADATION IN THE LENS Principal Investigator & Institution: Duvoisin, Robert M.; Associate Scientist; Ophthalmology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2001 Summary: The nucleus and organelles of lens fiber cells are degraded during cell differentiation. Because light would be scattered by these membranous particles, this process is necessary for clear vision. Very little is known about the biochemical and cellular mechanisms of this degradation and their regulation. A similar phenomenon occurs in reticulocytes, precursors of red blood cells. Following nucleus expulsion, organelles, including mitochondria and endoplasmic reticulum, are degraded. It has been proposed for a number of years that this process involves lipoxygenase, an enzyme that dioxygenases arachidonic acid and other polyenoic fatty acids. Several mechanisms have been suggested, all based on lipoxygenase modifying organelle membrane lipids or membrane-associated proteins. We have accumulated data that support a totally new mechanism: we propose that the soluble enzyme lipoxygenase assembles into a multimeric structure that forms pores in the membranes of organelles. Such pores would allow the cytoplasmic protein degradation machinery to gain access to the lumenal compartment and initiate the degradation of the organelle. We also found that lipoxygenase is expressed in the lens, most strongly in the peripheral fiber cells where nucleus and organelle degradation occur. We hypothesize that organelle degradation in the lens uses a similar mechanism as in reticulocytes. This proposal will test this hypothesis by identifying the lipoxygenase isozyme expressed in lens, analyzing its regulation of expression, gaining a better understanding of how lipoxygenase permeates membranes, and studying the expression of lipoxygenase in animal model and human cataractous lenses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS OF PHOTORECEPTOR DEATH IN PHOTIC INJURY Principal Investigator & Institution: Dunaief, Joshua; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 01-JUL-2000; Project End 31-MAY-2005 Summary: Age related macular degeneration, the most common cause of blindness among people aged 50 and older in the United States, results in photoreceptor degeneration. Similarly, retinitis pigmentosa, retinal detachment and ischemic diabetic retinopathy all lead to photoreceptor death. The loss of photoreceptors is the ultimate

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Macular Degeneration

cause of significant visual loss. The mechanism of photoreceptor degeneration in these diseases is poorly understood, but is known to occur through apoptosis. This programmed cell death is a highly ordered and regulated cellular suicide pathway that has been well defined in lymphocytes. This application proposes to draw from the rich knowledge of apoptosis in lymphocytes to elucidate mechanisms of photoreceptor cell death in the photic injury animal model of retinal degeneration. This model has been studied extensively at the cellular but not yet at the molecular level. Good evidence suggests that photoreceptor degeneration in this model occurs through apoptosis. The ability of anti-apoptotic genes expressed in transgenic mice to inhibit photic injury induced cell death will be tested. Specifically, the ability of anti-oxidant genes and antiapoptosis genes that act upstream or downstream in apoptosis pathways to inhibit photoreceptor degeneration will be evaluated. Further, the intracellular localization of cytochrome c, a mediator of apoptosis, and the role of caspase activation will be probed. Caspases are proteases involved in a number of apoptotic pathways. These studies will define critical apoptotic pathways and suggest therapeutic interventions for the blinding disorders that result from photoreceptor degeneration. The proposed study is well within the realm of feasibility. The principal investigator has experience with molecular biology, transgenic mice and retinal histology. The mentor is an international leader in the molecular mechanisms of apoptosis, and the co- mentor has extensive experience with transgenic mouse models of retinal disease and gene therapy. This proposal should serve as a good launching pad for the PI's career devoted to understanding the molecular basis of photoreceptor degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MICROCONTACT ENGINEERING

PRINTER

FOR

OPHTHALMIC

TISSUE

Principal Investigator & Institution: Bloom, David M.; Alces Technology, Inc. 4265 Willowbrook Ln Wilson, Wy 83014 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): This project will demonstrate a prototype microcontact printing aligner for use in ophthalmic tissue engineering. The performance of the microcontact printing aligner will be refined and validated by experiments conducted in collaboration with the Stanford Ophthalmic Tissue Engineering Laboratory. Functioning much like traditional rubber-stamping methods, microcontact printing is widely used to print molecules, such as growth factors or extracellular matrix proteins, in well-defined locations at the nanoscale. This project focuses on microcontact printing applied to a tissue engineering solution for age-related macular degeneration. Using microcontact printing on autologous lens capsule, the Stanford Ophthalmic Tissue Engineering Laboratory is developing a replacement retinal pigment epithelium for treating age-related macular degeneration. Current microcontact printing techniques depend strongly on the skill and ability of the researcher. A prototype tool will be built to improve the reproducibility of microcontact printing. This will require investigation into and enhancement of the stamping materials and techniques. Additionally, this tool will allow for printing of multiple layers, with alignment between the layers. A tool for aligned microcontact printing is a significant enhancement over the current techniques, and something that is neither commercially available, nor easily developed in most biological research facilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR BASIS OF SYNDROMIC RETINITIS PIGMENTOSA Principal Investigator & Institution: Hayflick, Susan J.; Associate Professor; Molecular and Medical Genetics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The goal of this project is to isolate and characterize the gene for a form of syndromic retinitis pigmentosa (RP), called Hallervorden-Spatz syndrome (HSS) and characterized by abnormal electroretinogram, lipofuscin accumulation in the retinal pigment epithelium, and early, rapidly progressive pigmentary retinopathy. This autosomal recessive disorder of childhood includes extrapyramidal dysfunction with iron accumulation in the basal ganglia. Though lipid peroxidation is an hypothesized mechanism leading to the HSS phenotype, no knowledge exists of the molecular or biochemical defect. We propose a molecular genetic approach to understanding this syndromic form of RP. Our specific aims are to 1) identify the gene for HSS, designated NBIA1 (Neurodegeneration with Brain Iron Accumulation, type 1) by completing the physical map of the critical region, identifying and screening candidate genes, and demonstrating deleterious mutations; 2) develop the molecular diagnosis of HSS using mutation studies and genotype-phenotype correlation; 3) characterize the HSS gene and its protein product at the tissue, cellular, subcellular and molecular levels using homology to model organisms, sequence analysis, histopathology, immunohistochemistry and studies of tissue expression patterns; and 4) isolate the murine homolog of the HSS gene and develop a mouse model for HSS in order to study its pathophysiology. Knowledge about the HSS gene will allow molecular diagnosis in individuals suspected to have this disease. As well, prenatal diagnosis of this fatal condition will be feasible. By delineating the pathophysiologic process in HSS, we may begin to develop rational therapies, which may be of benefit in treating other forms of RP, as well. Rare diseases often illuminate the mechanisms at work in common, related disorders. An advantage to studying syndromic RP is that the pleiotropic manifestations provide a context to help delineate the mechanism of retinopathy. The HSS gene is not retina-specific, and a defect in it must account for rod photoreceptor degeneration as well as regional brain iron accumulation. Furthermore, since defects in this non-retinaspecific process may cause other forms of syndromic and isolated RP and may be integral in disorders of lipofuscin accumulation, including aging macular degeneration, identification of the HSS gene may lead to greater understanding of RP as well as the macular dystrophies associated with senescence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR MECHANISMS UNDERLYING OPTIC NERVE REGENERATION Principal Investigator & Institution: Chen, Dong F.; Assistant Professor; Schepens Eye Research Institute Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2005 Summary: (Verbatim from applicant's abstract): The long-term objective of this research plan is to elucidate the molecular mechanisms underlying nerve growth and regeneration. It is generally believed that neurons in the brain and retina of mammals are unable to regenerate nerve fibers, which presents a great challenge for the treatment of retinal degenerative disorders and damage. Recent data have established that retinal ganglion cells (RGCs) are intrinsically regulated in their ability to extend nerve fibers, and that the proto-oncogene Bcl-2 is a key regulator supporting the mechanism for nerve elongation. This growth-stimulating activity of Bcl-2 does not seem to be a

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Macular Degeneration

consequence of its well-known anti-apoptotic function. The central question here is the mechanisms by which Bcl-2 promotes the regeneration of retinal nerve fibers. It has long been recognized that neural differentiation impacts nerve growth. It is now evident that overexpression of Bcl-2 suppresses the function of a differentiation signal, p53-mediated transcriptional activation, and expression of terminal differentiation markers in neurons. Therefore, it is hypothesized that Bcl-2 may function as a repressor of the p53-p21WAF1 pathway inhibiting neural terminal differentiation and thus, maintaining the ability of RGCs to grow nerve fibers. Using genetically-engineered mouse models as well as novel retinotectal co-cultures, this research plan is aimed at elucidating functional pathway(s) through which Bcl-2 may support optic nerve regeneration. Our goals are: (1) to investigate whether Bcl-2 inhibits the terminal differentiation of RGCs by determining levels and timing of RGC markers and differentiation-related protein expression in retinas of wild type and Bcl-2 mutant mice; (2) to test whether Bcl-2 supports nerve regeneration via suppression of the differentiation signal, p53-p21WAF1 pathway. Here, functional interactions between Bcl-2 and p53 will be assessed by comparing transcriptional activity, subcellular localization, and phosphorylation of p53 in wild type, Bcl-2 mutant, and Bcl-2/p53 double mutant mice; and (3) to determine whether Bcl-2 acts on a common cellular pathway to support nerve regeneration and neuronal survival by comparing the ability of RGCs from Bcl-x, and Bcl-2 transgenic mice to survive and regenerate nerve fibers. Given the functional importance of Bcl-2 in neuronal survival and nerve regeneration, these studies should provide valuable information for the development of neuroprotective drugs and therapeutic strategies for numerous diseases mediated by dysregulated cell death and nerve growth, including glaucoma and macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR RISK FACTORS FOR AGE-RELATED MACULOPATHY Principal Investigator & Institution: Schaumberg, Debra A.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): This is a revised application by a new investigator to assess the role of inflammation in age-related maculopathy (ARM). ARM comprises the leading cause of incurable blindness among older adults in the US and other developed countries. However, the basic molecular pathways involved in the pathogenesis of ARM remain unknown, few potentially modifiable risk factors have been identified, and treatment remains inadequate. We hypothesize that the pathologic changes occurring in both the early and late stages of ARM are mediated by cells and molecules associated with inflammation and that the pro-inflammatory state that gives rise to these changes is at least in part a systemic rather than merely local phenomenon. The proposed studies will build upon a broadly based and growing body of research that supports a key role for inflammatory/immune-mediated processes in ARM pathogenesis. This research suggests several pathways through which inflammation could mediate the development of ARM, including RPE damage and repair, drusen formation, degeneration of Bruch's membrane, endothelial dysfunction in choroidal vessels, increased oxidative stress, decreased bioavailability of antioxidants, as well as the direct or indirect promotion of angiogenesis. Through its use of archived blood specimens from the Physicians' Health Study, Women's Health Study, women's Antioxidant Cardiovascular Disease Study, Nurses' Health Study, and Health Professionals Follow-up Study, this proposal represents an exceptionally cost-effective and efficient means to investigate the proposed hypothesis using a prospective nested case-control study design. The Specific

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Aims are to investigate 1) the relationship of systemic markers /mediators of inflammation (IL-6, C-reactive protein, fibrinogen, haptoglobin, circulating adhesion molecules, and tumor necrosis factor-alpha receptors) with incident ARM, 2) the separate relationships of these inflammatory molecules with dry and neovascular ARM lesions, 3) whether the relationship of inflammation with ARM is independent of other risk factors such as cigarette smoking, and 4) the interrelationships among the biomarkers and which independendy predict incident ARM. These aims will be accomplished through measurement using highly sensitive assays of inflammatory biomarkers in blood specimens collected at baseline (i.e. prior to the development of ARM) and stored since that time below -80xC. Biomarker levels will be compared among subjects who eventually developed ARM and control subjects who remained free of ARM, and the analysis will be extended to control for other risk factors. The longterm objective and clinical relevance of this research is to shed light on potential underlying biological mechanisms of ARM pathogenesis and suggest avenues for new preventive or therapeutic approaches, as well as to identify clinically useful biomarkers for identification of individuals at increased risk of ARM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR STUDIES OF RETINAL DEGENERATION IN DROSOPHILA Principal Investigator & Institution: Colley, Nansi J.; Associate Professor; Ophthalmology and Visual Sci; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-JUL-2005 Summary: (provided by applicant): The objective of the proposed research is to utilize Drosophila as a model for studying hereditary human diseases that cause retinal degeneration and eventual blindness [retinitis pigmentosa (RP) and age-related macular degeneration (AMD)]. The complexity and variations of human RP and AMD suggest that there are multiple subtypes of the diseases, each with distinct genetic and biochemical bases. This complexity, the infrequent availability of ocular tissues from RP and AMD patients, and the broad base of knowledge of Drosophila molecular genetics, combine to make Drosophila a powerful animal model for studying inherited retinal degeneration disorders. We propose to use an integrated strategy of biochemical, cell biological, electrophysiological, genetic, and molecular approaches to identify and characterize mutations that cause defects in protein transport and targeting. We have identified three mutant lines of flies that display secretory pathway defects and retinal pathology. We will identify the corresponding genes and subject them to a detailed genetic and molecular analysis. In addition, we will continue to screen 12,000 individual mutant lines for retinal degeneration. The screen is based on a simple morphological phenotype that may be screened in live flies under the dissecting microscope. Mutants that define constituents of the secretory pathway and protein targeting will be subjected to a detailed characterization. Our findings will be utilized to screen a highly defined set of human AMD and RP patients for similar defects. Genetic analysis in Drosophila remains a powerful means of rapidly identifying genes that are essential for protein trafficking and normal photoreceptor function. It is anticipated that genes identified in this study will provide insights for the genetics of AMD and RP in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Macular Degeneration

•

Project Title: MRI PROBES FOR MAPPING RETINAL ACTIVITY IN VIVO Principal Investigator & Institution: Louie, Angelique Y.; Biomedical Engineering Div; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (Applicant?s Abstract) This proposal describes the development of probes for three-dimensional imaging of retinal activity. These probes are magnetic resonance imaging (MRI) contrast agents that are sensitive to membrane potentials. It is the signal from water protons that provides the image in typical MRI images and contrast agents interact with water to enhance that signal. In our previous work we have shown that by blocking the interaction of water with the contrast agent we can "turn off? enhancement, and then selectively "turn on" enhancement by removing the block. In these previous experiments we added a blocking group to the contrast agent that is removable by enzyme cleavage, so that signal enhancement was dependent upon enzyme cleavage. Based on these results we hypothesize that we can modulate the ability of an agent to enhance MRI signal by adding a group that is sensitive to membrane potentials, thus making signal enhancement dependent on membrane activity. In our research design we propose to: 1) Design and synthesize an agent based on a known optical indicator of membrane potentials 2) Characterize the ability of the new agent to enhance contrast in cell-free and cell culture systems. 3) Perform studies leading to the application of the new agents in eyes in vivo. These studies include determining the optimal route of delivery for the agent, and its biodistribution in model animal studies. These investigations will ultimately be extended to rodent models of retinal degeneration to map the loss of retinal activity over time and correlate the results with those observed by traditional methods. Results of the proposed studies will provide a noninvasive method to image membrane activity in deep tissues; this may aid in the early diagnosis of retinal disease. While our ultimate goal is to apply these agents in studies of macular degeneration, these agents would be useful for observations of any system in which membrane signaling activity plays a role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MULTI-AGENT CLASSIFICATION

COLLABORATION

FOR

AMD

SUBTYPE

Principal Investigator & Institution: Williams, Andrew B.; Electrical and Computer Engineering; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): Age-related macular degeneration (AMD) is the most common cause of blindness in developed countries and as such represents a very significant public health problem a number of specific genes, and the discovery, characterization, and eventual therapeutic control of these genes represent major goals of the vision research community. Although the strategies for gene discovery have become very powerful in recent years, there remains a major obstacle to the discovery of genes that underlie common, late-onset diseases like AMD. That obstacle is that clinicians cannot reliably sort patients with different molecular subtypes of late-onset disease into sufficiently homogeneous groups. The purpose of this project is to use the power of multi-agent systems computer technology in a novel way to aid clinicians in the collaborative development of a robust classification system based upon the ophthalmoscopic features of AMD. The result of this project will contribute to an NIH's Innovations in Biomedical Information and Science and Technology Program goal of speeding the progress of biomedical research through the development tools for

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electronic collaboration that will have impact on broader areas of biomedical research. We hypothesize that a multi-agent approach to this problem will result in a classification system with greater reproducibility and discriminative power than a system developed by clinicians without such computer assistance. The availability of populations of AMD patients with lower molecular complexity will significantly increase the power of statistical techniques for AMD gene discovery. In addition to this immediate and specific benefit, the strategies we will develop during this project for objectively interfacing medical experts with each other as well as with computers will have applications in the search for other late-onset disease genes as well as in the development of multi-center and multidisciplinary clinical trials of new therapeutic approaches. The proposed system, the Intelligent Distributed Ontology Consensus system (IDOCS) goes beyond conventional groupware by addressing drawbacks to direct, synchronous interaction by providing an autonomously coordinated, asynchronous interaction and collaboration platform among clinicians through their representative intelligent agents. IDOCS will provide a generic meta-data infrastructure using XMLJRDF to make it easily configurable for other diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPHTHALMIC IMAGING USING ADAPTIVE OPTICS AND OCT Principal Investigator & Institution: Werner, John S.; Professor; Ophthalmology; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): The purpose of this BRP is to develop and evaluate new instrumentation that will permit unprecedented three dimensional imaging of single cells in the human retina, specifically rod and cone photoreceptors and ganglion cells. An interdisciplinary team will combine adaptive optics (AO), enabling the best lateral resolution for retinal imaging, with optical coherence tomography (OCT), providing the best axial resolution for retinal imaging. Two instruments will be developed using complementary OCT imaging modalities, flood illumination and enface scanning. These instruments will be used to study cellular morphology associated with normal aging, age-related macular degeneration (AMD) and glaucoma. The instruments will be compared quantitatively with each other and with existing retinal imaging devices. The project will be led by UC-Davis COCD), where a highperformance AO system has been developed in collaboration with the Lawrence Livermore National Laboratory (LLNL). This collaboration will be expanded to include a team of OCT experts at LLNL and Indiana University (IU). The IU team has previously collaborated with LLNL through the Center for Adaptive Optics and has already developed a working prototype AO-OCT system for retinal imaging. In this BRP project, LLNL will construct one AO-OCT instrument at the UCD site to be tested clinically in years 3-5, while the second AO-OCT instrument will be developed at IU in collaboration with LLNL and tested in the laboratory in years 4-5. Comparisons of AO-OCT and functional measures will be obtained at UCD and IU. Both instruments will be made available for use by scientists and clinicians who are not part of the BRP, and will be refined through the course of the project period. UCD has expertise in vision science, aging, and evaluation of AMD and glaucoma progression and treatment LLNL has a long history of research on AO for astronomy and has transferred some of its AO technology to vision science at UCD. LLNL also has expertise in OCT, and has pioneered its application to in vivo imaging of oral and vascular structures. The IU team has experience in AO-OCT and vision science with specific expertise in visual optics and retinal electrophysiology. This BRP is buttressed by consultants who have developed

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Macular Degeneration

ophthalmic OCT technology at the University of Texas and Carl Zeiss Meditec. The Zeiss group has already transferred OCT technology to the clinic via commercial development and will facilitate incorporation of user friendly interfaces for our AOOCT systems. This BRP thus combines the unique expertise of engineers, vision scientists and clinicians who have experience working together to effect a smooth transition from the laboratory to applications. This synergistic team will develop a new generation of instruments to advance vision science, permit retinal dysfunction to be studied in vivo in a way that will offer new insights into normal aging, the pathogenesis of glaucoma and macular degeneration, and a reliable method to monitor novel treatments for retinal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: OPSINS, G PROTEIN PATHWAYS AND REGULATION IN RPE CELLS Principal Investigator & Institution: Fong, Henry K.; Doheny Eye Institute 1450 San Pablo St Los Angeles, Ca 90033 Timing: Fiscal Year 2001; Project Start 01-AUG-1990; Project End 31-JUL-2002 Summary: (Adapted from applicant's abstract): Vertebrate RPE and Muller cells contain a cytoplasmic visual pigment homolog termed RGR (for RPE retinal G protein-coupled receptor) which binds retinoid and shares sequence similarity with retinochrome, a photoisomerase in squid photoreceptors. This application hypothesizes that RGR may function as a retinal isomerase in the vertebrate visual cycle, be involved in a primitive form of phototransduction, play a role in circadian rhythm, or act as a sensor of free retinaldehyde. To test these hypotheses, research will investigate RGR ligand- and protein-binding properties and analyze the phenotype resulting from mutation of the RGR gene in a RGR-less mouse model system. The endogenous chromophore of bovine RGR will be identified and photoisomerization of retinal bound to natural and recombinant RGR will be investigated. A splice variant of the human RGR gene termed RGR-d has been identified in which the predicted sixth transmembrane domain is deleted. To investigate the possibility that RGR-d is involved in diseases of the retina such as age-related macular degeneration (AMD), studies will characterize human RGR-d retinaldehyde-binding properties, subcellular localization and other possible altered properties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: P27KIP1 AND RPE CELL CYCLE Principal Investigator & Institution: Defoe, Dennis M.; Anatomy and Cell Biology; East Tennessee State University Box 70565 Johnson City, Tn 37601 Timing: Fiscal Year 2003; Project Start 04-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Abnormal growth or turnover of the retinal pigment epithelium (RPE) is associated with an alarming number of ocular disorders (i.e., proliferative vitreo-retinopathy (PVR), age-related macular degeneration, developmental hamartomas, congenital hypertrophy of the RPE), accounting for significant health costs. An understanding of the basic mechanisms for establishing and maintaining appropriate epithelial cell number and size is crucial to finding ways to alleviate disease consequences and to facilitate their repair. The aim of the proposed research is to define the mechanisms that regulate growth, through cell multiplication and enlargement of cell size, during RPE development in situ. While many exogenous influences can regulate cell proliferation, they do so by ultimately impinging on

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machinery of the cell division cycle. Consequently, the proposed studies focus on mechanisms operating in the RPE cells as they withdraw from the cell cycle during differentiation of the epithelial layer in vivo. Experiments will make use of a mutant mouse with targeted disruption of the gene coding for the cell cycle regulatory protein p27Kip1, in which there is an abnormal expansion of the RPE rnonolayer. The overall hypothesis is that loss of p27Kip1 leads to an increase in the number or density of epithelial cells as a result of an enhancement in the rate of cell proliferation, or of a delay in the timing of cell cycle exit prior to differentiation. This hypothesis will be tested using immunohistochemical techniques to determine the magnitude of cell division, as well as cell death, at various developmental ages. The alternative hypothesis that the thickening of the RPE layer is due to an increase in cell size will be examined by morphometric analysis of images obtained by confocal microscopy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PEDF AND PHOTORECEPTOR PROTECTION: A NAKED DNA APPROACH Principal Investigator & Institution: Cao, Wei; Ophthalmology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): PEDF and photoreceotor protection: a naked DNA approach. Photoreceptor cell death is an irreversible event in many blinding diseases including retinitis pigmentosa, age-related macular degeneration and retinal detachment. Pigment epithelium derived factor (PEDF), a secreted protein with both neurotrophic and anti-angiogenic properties, is made in vivo by a variety of cells in both fetal and adult animals. Within the retina, it is secreted by retinal pigment epithelial (RPE) cells into the interphotoreceptor matrix, placing it in a prime physical location to affect the underlying photoreceptor cells. We recently reported that the intravitreal injection of PEDF protected photoreceptor cells against constant light induced damage in a rat model. An alternative method for delivering a protein factor to cells and tissues is to use only the DNA which codes for the protein. Our preliminary data show that primary cell cultures of rat retinal neurons can be transfected with a naked DNA coding for enhanced green fluorescent protein under the control of the photoreceptor cellspecific promoter, mouse interphotoreceptor retinol binding protein. We have performed similar experiments expressing other reporter genes under control of other photoreceptor cell specific promoters. These experiments suggest that we are able to transfect PEDF cDNA into retinal neurons which will then express the PEDF protein. I am seeking three years of funding in this proposal to develop a novel approach using plasmid DNA cassettes expressing PEDF and apply it to the retina to prolong useful vision by delaying or preventing retinal degeneration. This novel method is actually being employed in phase I clinical trials with the injection of a naked DNA encoding the angiogenesis factor, VEGF, into the hearts of cardiac patients. In several phase II trials, direct injection of DNA has also demonstrated significant therapeutic effects in cancer patients. The specific aims of this proposal are: I) To demonstrate the expression and protection efficiency of transfected naked plasmid DNA, encoding PEDF, in cultured rodent retinal cells. 2) To maximize the in vivo expression of naked plasmid PEDF in the eye, through the optimization of the route of administration, such as topical application, anterior chamber/intravitreal/subretinal injection. 3) To evaluate the protective efficacy of this protocol to prevent the retinal degeneration induced by light or by heredity. The proposed studies are innovative and could have a significant clinical impact as a novel

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Macular Degeneration

therapeutic approach to delay or prevent retinal degeneration and to prolong useful vision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PHOTORECEPTOR TRANSDUCTION

CELL

DEVELOPMENT

AND

SIGNAL

Principal Investigator & Institution: Carthew, Richard W.; Professor; Biochem/Molecular & Cell Biol; Northwestern University 633 Clark St Evanston, Il 60208 Timing: Fiscal Year 2003; Project Start 01-MAR-1993; Project End 31-JUL-2006 Summary: (provided by applicant): Growth factors are important signaling proteins that control cell growth, survival, and differentiation in the developing and adult retina. The ultimate objective of the proposed research is to understand the molecular mechanisms that growth factors use to regulate cell behavior in the retina. We address this question by studying the differentiation of photoreceptor and cone cells in the Drosophila eye that are regulated by growth factor ligands for the Sevenless and EGF Receptor Tyrosine Kinases. This could provide important insights into how retinal cell differentiation is regulated, and how errors in growth factor signal transduction can lead to retinal diseases such as macular degeneration and retinitis pigmentosa. A paradox of growth factor signaling is how cells respond so specifically to a signal that appears to carry little informational content. For example, the Pros gene becomes transcriptionally activated as an immediate-early target of EGFR in a subset of cells (R7 and cone) that are activated by EGFR. A combinatorial mechanism restricts Pros enhancer responsiveness to EGFR activation. Other required inputs include two transcription factors (Lola, Lozenge) and a cell-cell signal mediated by the Notch Receptor. Pros transcription increases specifically in the R7 photoreceptor where it is required for its proper differentiation. The mouse homolog of Pros, Prox-1, is also required for proper development of the eye. The R7specific transcriptional response requires activation of the Sevenless receptor, which induces expression of another immediate-early gene, Phyllopod. Phyllopod associates with a transcriptional repressor called Tramtrack, and this results in ubiquitination and degradation of Tramtrack protein. Tramtrack destruction may be the sole essential action of Sevenless to activate Pros. Our approach has been to characterize molecular interactions between proteins in the GFR/Sevenless pathways and a target gene, Pros. As such, Pros serves as an experimental model gene. We use a combination of genetic and biochemical experiments. The goal of the proposed research is to further characterize EGFR and Sevenless signaling by: 1) determining how other signals like Notch integrate with the EGFR signal to regulate Pros, 2) determining how EGFR and Sevenless exert different effects on Pros transcription, 3) characterizing a second model target gene, Phyllopod, as a way to compare and contrast with Pros regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RECEPTORS

PILOT--CHEMICAL

PROFILING

OF

ORPHAN

NUCLEAR

Principal Investigator & Institution: Downes, Michael; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: A solid clinical rationale exists for the discovery of novel orphan nuclear receptor (ONR) therapeutic ligands. The intimate associate, for example, between PPARgamma and carbohydrate and lipid metabolism, for example, finds clear

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expression in a variety of metabolic and aging disorders from atherosclerosis and lipid metabolism, for example, finds clear expression in a variety of metabolic and aging disorders, from atherosclerosis and diabetes, to Alzheimer's disease, decreased skin elasticity, male erectile dysfunction, pulmonary fibrosis, and atherosclerosis, and ocular diseases such as diabetic retinopathy, glaucoma, cataract formation, and age-related macular degeneration (AMD). This proposal will focus on the discovery of novel chemical tools for the purpose of advancing ONR research. A technology platform will be assembled that will facilitate the screening of chemical compound libraries for molecules able to modulate ONR-mediated transcription. Chemical screens that will be established to achieve this objective will consist of both in vivo and in vitro bas assays developed specifically for a high throughput (HTS) 384 well format. The assays developed exploit the agonist induced association of receptor ligand binding domains (LBDs) with nuclear receptor co-regulators and their derivative peptides. Currently we have diverse 18000 chemical compound library of mostly synthetic compounds that we have demonstrated to be viable for screening against ONRs. A pilot a screen of these compounds against FXR and identified novel compounds that robustly activate transcription of this ONR. The major goal of this project is to identify potent, specific compounds and make them freely available to the academic community to contribute high quality and unrestricted research on ONR function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PREVENTING DEPRESSION IN MACULAR DEGENERATION Principal Investigator & Institution: Rovner, Barry W.; Psychiatry and Human Behavior; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2001; Project Start 06-FEB-2001; Project End 31-JAN-2006 Summary: Applicant's This application describes a randomized controlled clinical trail to evaluate the efficacy of a brief, standardized cognitive psychotherapy, Problem Solving Therapy (PST), to prevent incident depressive disorder (DSM-IV diagnoses) in elderly patients with age-related macular degeneration (AMD). AMD is the most common cause of blindness in older adults and limits the ability to read, see familiar faces, and walk independently. Almost 2 million persons (about 5 percent of the U.S. population over age 65) are now affected and their number will triple by the year 2020. We will target patients with neovascular AMD (NV-AMD), a form of AMD that can lead to sudden vision loss, substantial disability, and depression. Because depression is itself disabling and not likely to be recognized nor treated by ophthalmologists, preventing depression is clearly important. We will recruit 230 non-depressed AMD patients from the retinovascular clinic of Wills Eye Hospital with newly diagnosed NV-AMD one eye, who already have AMD in the fellow eye. Because they have recently developed bilateral vision loss they will be at high risk for depression. We will randomize subjects to PST or a usual care control condition in this 6-month clinical trial. The primary outcome measure will be a DSM-IV diagnosis of depression diagnosed by a geriatric psychiatrist masked to treatment assignment. We will evaluate subjects at baseline, month 2 (immediately post-intervention), month 6 (for the primary efficacy analysis) and month 12 (to evaluate sustained effects). Although depressive disorder is the primary outcome, we will also assess the impact of PST on levels of disability and vision-related quality of life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROSPECTIVE STUDY OF RISK FACTORS FOR EYE DISEASE Principal Investigator & Institution: Hankinson, Susan E.; Associate Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-JAN-1995; Project End 31-DEC-2004 Summary: We propose to investigate several lifestyle and genetic factors in relation to age-related macular degeneration (AMD) and primary open angle glaucoma (POAG) in two prospectively followed cohorts of women and men. Specifically, we will evaluate dietary intake of antioxidants and fat (including specific types of fat), postmenopausal hormone use and variants in the ATP-binding cassette-transporter retina (ABCR) gene in relation to both wet and dry AMD, and antioxidant intake, smoking, and systemic blood pressure in relation to POAG. The Nurses' Health Study (NHS) began in 1976 among 121,700 women ages 30-55 at that time. About 89,000 participants completed an extensively validated semiquantitative food frequency questionnaire (FFQ) in 1980 and every 2-4 years since. The Health Professionals Follow-up Study (HPFS) began in 1986 among 52,000 men ages 45-75, all of whom completed a FFQ at baseline and every four years since. Both groups have been sent a questionnaire biennially to update exposure information and reports of major illnesses, including AMD and POAG. Information has been collected repeatedly on specific vitamin supplement use, smoking, diagnosis of hypertension, reported blood pressure, and postmenopausal hormone use among other factors. Over 32,000 blood samples were collected in the NHS in 1989-90 and over 18,000 in the HPFS in 1993. In the proposed study we will confirm reports of AMD and POAG by contacting the participant's ophthalmologist, and obtaining detailed information from the optical record, including fundus photographs for those with AMD. A case will be considered to have AMD if it is judged to be sufficient to result in a visual acuity loss of at least 20/30 and is confirmed by a standardized review of the fundus photograph; wet and dry types will be carefully delineated by photographic review. A case will be considered to have POAG if confirmed by medical record review and is documented to have visual field loss. We anticipate 554 cases of exudative and 833 cases of dry AMD, and 1049 cases of POAG. Stratified and multivariate techniques will be used to quantify the risk of AMD and POAG according to the level of exposure after controlling for potentially important confounders; analyses will be conducted among participants who reported having a recent eye exam. Overall, the prospective design, large size of the cohorts, the high follow-up rates, repeated exposure measures, and carefully confirmed disease definitions provide a unique opportunity to evaluate several hypotheses of public health importance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PROTEIN PRODUCTION OF PEDF-POTENT ANTIANGIOGENIC AGENT Principal Investigator & Institution: Wei, Lisa L.; Genvec, Inc. 65 W Watkins Mill Rd Gaithersburg, Md 20878 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-OCT-2003 Summary: (provided by applicant): Exudative age-related macular degeneration (AMD) and proliferative diabetic retinopathy (DR), due to aberrant choroidal and retinal neovascularization respectively, are two of the leading major causes of blindness in the US. PEDF (Pigment Epithelium-Derived Factor) is a potent endogenous antiangiogenic/neurotrophic factor and is purported to be the key natural regulator of vascularity in the eye. In experimental disease models, PEDF blocks choroidal and retinal neovascularization. Based on these compelling data, we hypothesize that

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administration of PEDF protein may treat blinding ocular neovascular diseases such as wet AMD. It will be the overall goal of the SBIR Phase II to generate preclinical data enabling potential clinical testing of PEDF protein. In this Phase I application, we will test the feasibility of generating PEDF for preclinical studies. We propose: 1) to generate reproducible stocks of high quality PEDF protein and 2) to demonstrate the biological activity/potency of the purified protein product. This bioactive recombinant human PEDF will be used for future PEDF pharmacokinetic studies, to test efficacy of purified PEDF protein in ocular disease models, to test various delivery approaches, and to determine whether PEDF-based product should be advanced to clinical testing. Furthermore, the methods and procedures generated in the Phase I SBIR grant may lead to future viable manufacturing processes and assays that could lead to clinical grade material. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PROTEOMIC DEGENERATION

STUDIES

OF

AGE

RELATED

MACULAR

Principal Investigator & Institution: Crabb, John W.; Professor and Staff Manager; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): The long-term goal of this research is to understand the molecular mechanisms of drusen formation and Bruch's membrane thickening in age-related macular degeneration (AMD). The unifying hypothesis is that protein modifications are causally involved in both processes. Drusen are extracellular deposits that form between the retinal pigment epithelium and Bruch's membrane and confluent drusen are the hallmark risk factor for developing AMD. The progression of AMO might be slowed or halted if drusen and Bruch's membrane changes can be modulated. The proposed research will identify proteins and lipids in drusen and Bruch's membrane from healthy and AMD donor tissues and characterize associated protein modifications and reactive lipid fragments. Four specific aims will test the following hypotheses: (i) that the drusen proteome differs among drusen sub-types; (ii) that the Bruch's membrane proteome varies with age and state of health; (iii) that lipid oxidation products in drusen and Bruch's membrane vary with age and state of health; (iv) that oxidative protein modifications contribute to drusen formation and Bruch's membrane thickening. Mass spectrometric methods will be used to identify and characterize proteins, phospholipids and lipid oxidation products. Immunocytochemistry will be used to confirm protein localization to drusen and Bruch's membrane. Western analyses, electrophoretic mobility shifts and bioinformatic tools will be used to detect protein modifications. The results will help establish a firm link between oxidative damage and the pathogenesis of AMD and provide new opportunities for developing strategies and therapies for preventing or limiting the complications of AMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: QUANTIFICATION OF DRUSEN IN MACULAR DEGENERATION Principal Investigator & Institution: Friberg, Thomas R.; Professor; Ophthalmology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2004 Summary: (Applicant's Abstract) Age-related macular degeneration (AMD) is the most common cause of blindness in the United Sates in Americans over the age of 50. Drusen are by-products of rod and cone metabolism and their presence in the ocular fundus is a

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Macular Degeneration

clinical sign of AMD. It is known that patients whose eyes harbor drusen are at special risk of visual loss from AMD. In a prospective, multi-centered trial, the Age-Related Eye Disease Study (AREDS), some 5000 patients have been enrolled and followed at sixmonth intervals to determine risk factors for AMD as well as to measure the influence of certain multivitamins and micronutrients on the progression of macular degeneration and cataract. In another prospective, randomized, controlled trial, the Prophylactic Treatment of AMD Trial (PTAMD), patients with multiple large drusen have been enrolled to determine whether a minimal laser treatment applied one time provides any benefit with respect to lowering rates of visual loss and rates of development of choroidal neovascularization (CNVM). During the PTAMD and AREDS trials, photographs of the fundi of each participant have been taken at least annually in the form of Ektachrome color slides. These slides are evaluated by human readers in a Reading Center and the extent of the drusen is categorized accordingly. The applicant proposes to perform a quantitative analysis on the color slides of the macula of all patients who have been enrolled into the PTAMD and AREDS trials at the Pittsburgh site, as well as other patients who have AMD and have been followed similarly for a minimum of three years. The original slides will be digitized onto CD disks for permanent archiving, and will be analyzed using a specially-written computer algorithm which semi-automatically detects drusen in digital images. Once detected, quantitative measurements of the area of drusen extent and size of each drusen are generated for each image. This method is more precise than characterizing drusen using traditional long and more subjective protocols, and may be valuable in determining the risks of a given patient developing choroidal neovascularization and visual loss before such events occur. That is, such continuous quantitative data may, when analyzed, provide a more accurate and sensitive assessment of risk compared to conventional measurement techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REACTIVE OXYGEN-INDUCED DNA DAMAGE IN RETINAL CELLS Principal Investigator & Institution: Godley, Bernard F.; Senior Scientist; Ophthalmology and Visual Scis; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 31-JUL-2001 Summary: This project examines the hypothesis that reactive oxygen intermediates (ROI) overwhelm declining antioxidant defenses in aged RPE leading to mitochondrial DNA damage, cell dysfunction and death. This chain of events may be a primary mechanism of aging and of acquired retinal diseases such as AMD. A major objective of this study is to assess the basal levels, formation and repair of oxidative DNA damage in nuclear and mitochondrial DNA in primary RPE cells obtained from young versus aged human donors. We will test the hypothesis that mitochondrial DNA damage may accelerate the production of ROI that leads to further damage and functional decline. The following specific aims will be addressed to meet the objectives of this proposal: 1) To examine the formation and repair of oxidative DNA damage from rod outer segment-fed human retinal pigment epithelium (RPE) cell cultures; 2) To elucidate the temporal sequence and downstream cellular consequences in oxidant- exposed cultured human RPE cells in relation to mitochondrial DNA damage, mitochondrial transcription and function, and cell death; 3) To evaluate the linkage between reactive oxygen intermediates (ROI), antioxidant enzyme systems, and oxidant-induced DNA damage; 4) To study the relevance of the glutathione S-transferase pathway in protecting RPE cells under oxidative stress: a study with mGSTA4-4 transfected cells; 5) To examine the

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formation of mitochondrial DNA damage and repair kinetics in RPE from aged human eyes, and eyes with AMD. Successful accomplishment of these specific aims will provide fundamental mechanistic insights regarding the molecular pathobiology of reactive oxygen in aging RPE cells. The ultimate goal of this project is to reveal and test novel clinical strategies to reduce morbidity from age- related macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: READING IN PERIPHERAL VISION Principal Investigator & Institution: Chung, Susana T.; Associate Professor; None; Indiana University Bloomington P.O. Box 1847 Bloomington, in 47402 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: (Adapted From The Applicant's Abstract): This is a grant directed at the problem of reading in low vision patients. Specifically, the PI is interested in those cases where macular damage makes it necessary to read with peripheral retina. Reading is difficult under such conditions. Proposed research will investigate three hypotheses about the causes of that difficulty: Grouping/crowding effects are more damaging in the periphery. Consequently, Aim 1 seeks to minimize these effects. Peripheral representation of phase is inaccurate. Aim 2 will attempt to enhance reading speed by minimizing the need for phase information. Patients lack of practice with peripheral reading. Aim 3 will examine the effects of extensive practice with peripheral reading. Experiments will be carried out with normally-sighted subjects as well as with subjects having central scotomata. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RECOMBINANT H-VEGI AS AN ANTICANCER THERAPEUTIC Principal Investigator & Institution: Medynski, Daniel C.; Proteomtech, Inc. 5980 Horton St, Ste 405 Emeryville, Ca 94608 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Blocking or inhibiting blood vessel growth (angiogenesis) remains a critical focal point for anticancer drug development. Studies on Vascular Endothelial Growth Inhibitor (VEGI; TNFSF-15) secreted from human endothelial cells have demonstrated that it is a potent negative regulator of angiogenesis that induces growth arrest and apoptosis in endothelial cells. Unfortunately, because of a limitation in the quantity of VEGI obtained in this manner and the difficulty encountered in the production of the recombinant form of this protein, preclinical studies using systemically administered VEGI to assess its therapeutic potential as an anti-cancer or anti-angiogenesis agent have not been possible. In addition, despite a considerable effort, no commercial or academic laboratory has succeeded in producing large quantities of this valuable molecule. We have now developed a procedure to produce VEGI in E. coil. In this proposal, three specific objectives will be pursued: 1. In a small scale pilot study, a number of expression vector constructs encoding variants of the four isoforms of VEGI will be expressed in E. coil as inclusion bodies, purified, and refolded. They will then be tested in endothelial cell growth arrest assays to isolate refolded, biologically potent VEGI isoforms. 2. Expression, purification, and refolding of isoforms of VEGI already identified as biologically active in pilot studies will be pursued at a much larger scale. One hundred milligrams to gram quantities of highly purified biologically active VEGI isolated from E. coli inclusion bodies will be prepared for in vivo animal studies. 3. The active isoforms of VEGI will be utilized in rodent xenograft studies to determine if VEGI has a potent antiangiogenic or anticancer effect

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Macular Degeneration

when systemically administered. The long term objective of this study is to develop VEGI into an effective drug in diseases involving angiogenesis - particularly cancer, but also atherosclerosis and blindness (macular degeneration). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REMOVAL OF THE LIPOFUSCIN COMPONENT A2E FROM RPE CELLS Principal Investigator & Institution: Rodriguez-Boulan, Enrique; Ophthalmology; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2005 Summary: (provided by applicant): This project will develop methods to reduce the amounts of N-retinyledene-N-retinylethanolamine (A2E) in the retinal pigment epithelia (RPE). The excessive accumulation of this lipofuscin component contributes to the onset of age-related macular degeneration (ARMD). Thus, any methods that can remove A2E from the RPE will be useful in developing potential therapies to treat this disease. To test the efficiency of various methods to remove A2E from cultured RPE cells, we will use a fluorescence plate reader and fluorescence microscopy to measure both the intracellular concentration and the subcellular location of A2E. Initial results using an in vitro system have already identified several drugs which are capable of removing A2E from phospholipid membranes. Subsequent work will focus on delivering these drugs to the Iysosomes of RPE, the site of A2E subcellular accumulation. Recent evidence suggests that A2E impairs the ability of RPE to degrade phospholipids derived from phagocytosed outer segment. Each day, the RPE is presented with shed outer segment particles, and must complete the digestion of these particles before the next day. Any delay in the digestion of the OSphospholipids, which comprises more than half of the total OS mass, will result in the gradual accumulation of these phospholipids. Once the development of methods that can remove A2E is achieved, the effectiveness of these systems in restoring the ability of A2E-treated RPE to degrade OS phospholipids will be examined. A flourescence-based lipid degradation assay has already been developed in this lab. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RETINAL ANTIOXIDANT GENES INDUCED BY PHOTIC INJURY Principal Investigator & Institution: Chen, Lin; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The candidate, Lin Chen, is determined to become a physician scientist and devote herself to both patient care and vision research. Her immediate career goal is to become an independent investigator. Although she has completed her graduate training in both basic science and clinical medicine, she will greatly benefit from the mentored clinical scientist development award. During the award period, she will acquire new research skills such as microarray analysis and mouse genetics, and obtain further training in the responsible conduct of research, and in communication and networking. The Scheie Eye Institute provides an ideal research environment for the candidate's career development. Dr. Chen's mentor, Dr. Jean Bennett, has a long track record of training scientists at all levels. She and the six other eye research faculty in the Kirby Center for Molecular Ophthalmology are eager to support Dr. Chen's career development. These faculty members have expertise in ophthalmic molecular biology, histology, gene transfer, animal models of retinal

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degeneration, and animal ERG. The Kirby Center is a cohesive team of eye researchers with state-of-the-art equipment occupying an 11,000 sq. ft. floor in the heart of the Penn biomedical research community. The scientific objective of this proposal is to understand the role of oxidative stress in age-related macular degeneration, the leading cause of irreversible blindness in the elderly. Specifically, this proposal will investigate the role of natural antioxidant genes in the mouse photic injury model, a model of photo-oxidative photoreceptor injury, and in human AMD specimens. The research design will employ microarray analysis of differences in antioxidant gene expression in normal mouse retinas versus photic injury retinas and in AMD eyes versus normal agematched eyes. It will also use transgenic and knockout mice to investigate the role of ceruloplasmin, an antioxidant found in Dr. Chen's preliminary studies to be upregulated following photic injury. This information will help define the mechanisms by which the retina protects itself from oxidative stress, which is important in the pathogenesis of AMD, as demonstrated by the Age-Related Eye Disease Study. New information about the specific mechanisms of oxidative damage and natural antioxidant protection in the retina will suggest new agents for protection and treatment of patients with AMD, preserving their vision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINAL DEGENERATION AND CHLORIDE CHANNELS. Principal Investigator & Institution: Hartzell, H Criss.; Professor; Cell Biology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2007 Summary: (provided by applicant): The ability to read this page without magnification depends upon the integrity of the macula, a small region of the retina including the fovea. Macular degeneration is the leading cause of blindness in developed countries. Age-related macular degeneration (AMD) is a progressive degeneration of the macula that affects approximately 20% of individuals over the age of 65, but its causes remain unknown. The hypothesis driving this proposal is that CI currents play a role in phagocytosis of shed photoreceptor discs by the retinal pigment epithelium (RPE). Defects in this process can lead to macular degeneration as the result of accumulation of retinoids and lipofuscin pigment in the subretinal space. We propose that CI channels are important in normal phagocytosis because they are involved in the regulation of cell volume during ingestion of large quantities of outer segments. A variety of well-known CI channels including CFTR, CIC-2, CIC-3, and CIC-5 are expressed in RPE cells and recently it has been suggested that bestrophin, an RPE protein that causes Best macular dystrophy, is the founding member of a new family of CI channels. The goal of this project is to characterize the CI currents, especially bestrophin-mediated currents, that are expressed in RPE cells and to understand their function. There are three specific aims. (1) To determine the properties of bestrophin CI channels. We will test the hypothesis that bestrophins are subunits of a chloride channel by patch clamp analysis of heterologously expressed bestrophins. (2) To characterize chloride channels in RPE cells. This aim tests the hypothesis that several types of CI channels are functionally specialized for specific RPE functions. The strategy is to use whole-cell and patch clamp recording to characterize CI channels in RPE cells and to compare them to the properties of known CI channels, including bestrophin. (3) To determine the role of CI channels in photoreceptor disc phagocytosis. This aim will test the hypothesis that CI channels are important in phagocytosis of rod outer segments by RPE cells. This hypothesis will be tested by determining the effects of pharmacological inhibitors and antisense knockdown of CI currents on the phagocytosis of rod outer segments by RPE.

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Macular Degeneration

Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RETINAL GENE EXPRESSION IN LIGHT AND DARKNESS Principal Investigator & Institution: Weitz, Charles J.; Associate Professor; Neurobiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 01-AUG-2001; Project End 31-MAY-2004 Summary: (Applicant's abstract) Retinal sensitivity to light is controlled both by the level of illumination (light adaptation at the photoreceptor and network levels) and by an endogenous circadian clock. Considerable evidence suggests that broad and coordinated programs of gene expression underlie the changes in sensitivity driven by light and by the circadian clock, respectively, and that these programs overlap or converge in common pathways. Although there are sporadic examples of retinal transcripts regulated by light, a circadian clock, or both, there is as yet no comprehensive view of retinal gene expression in a natural light-dark cycle or in constant darkness. Microarray technology, developed for massively parallel analysis of gene expression, now permits detailed investigation of biological processes too complex for piecemeal approaches. Described here is a proposal to use cDNA microarrays to analyze gene expression in the mouse retina on a genome-wide scale. Two kinds of microarrays will be used for the analysis. The first contains 40,000 unique, fully sequenced mouse cDNAs, representing on the order of 50% of all mouse genes. The second is a custom microarray which will contain a few-thousand unique retinal cDNAs that encode secreted and transmembrane proteins, to be obtained in a large-scale "secretion trap" screen. This cDNA set will be highly enriched for molecules involved in intercellular communication, such as neuropeptides, receptors, and ion channels, known and unknown, likely to play a role in the control of retinal sensitivity. Retinal gene expression will be monitored at 4-hour intervals over two days, both from mice kept in a 24 hour light dark cycle and from mice kept in constant darkness. The incorporation of both conditions into a single experiment is a key-feature of the proposal. This experiment should provide comprehensive, parallel views of the dynamics of (i) diurnal gene expression over the course of a natural light-dark cycle and (ii) circadian clockregulated gene expression. The design will permit transcripts regulated by light to be distinguished from those regulated by a circadian clock, and it should provide insight into how the natural temporal pattern in a light-dark cycle arises from the interaction of a light-driven transcriptional program with a clock-driven one. Overlap between the two programs will likely highlight transcripts involved in changes in sensitivity of the retina to light. It is likely that a comprehensive view of natural retinal gene expression programs in light and darkness will provide deep insights into retinal physiology and open new avenues of inquiry regarding the coordinated responses of the retina to light. Aberrant transcriptional events are known to underlie light-induced photoreceptor degeneration, and knowledge of retinal gene expression programs will almost certainly stimulate progress in understanding retinal diseases such as age-related macular degeneration and retinitis pigmentosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: RETINAL IMAGE QUALITY IN RETINAL-DISEASED EYES Principal Investigator & Institution: Shahidi, Mahnaz; Ophthalmology and Visual Scis; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2005

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51

Summary: (provided by applicant): The optical properties of the eye and its imperfections limit visual performance, the ability for an individual to view the world, and retinal imaging, the ability for an ophthalmologist to view the retinal tissue. Recent advances in wavefront sensing and adaptive optics technologies have allowed measurement and correction of monochromatic wavefront aberrations in healthy human eyes. However, it is likewise important to investigate disease-related changes in the optics of the eye, since they can significantly contribute to degradation of both visual performance and resolution for retinal imaging. Particularly, there is a need to differentiate between vision loss that results from retinal disease and visual performance that is impaired due to imperfect optics, in order to anticipate optimal outcome for therapies applied to improve neural function of the retina in eyes with imperfect optics, or to foresee consequences of procedures that are targeted to improve the optical property of eyes with diseased retinas. Equally important is a need for high-resolution imaging of the retinal tissue that may be achieved by compensation for ocular aberrations with the use of adaptive optical components and image processing methodologies. Such imaging would allow visualization of fine retinal structures, thus providing for better understanding of retinal pathophysiology and enhanced diagnostic evaluation of retinal diseases. In the current research proposal, our novel technique for optical section retinal imaging will be coupled with wavefront sensing technology. Imaging will be performed in subjects diagnosed with diabetic retinopathy and agerelated macular degeneration and the optical performance of retinal-diseased and healthy eyes will be compared. The relation between ocular aberrations and retinal imaging resolution will be determined. High-resolution retinal imaging will be achieved by compensation for ocular aberrations. Findings from the research study will provide knowledge on the nature and extent of disease-related changes in the optical properties of the eye, that is of value for evaluation of optical factors that contribute to degradation of visuai performance and for achievement of high-resolution retinal imaging in subjects with retinal diseases that are considered the most prevalent causes of blindness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF PI3 KINASE AND ITS DOWNSTREAM TARGET BCL-XL IN RPE Principal Investigator & Institution: Le, Yun Zheng; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2007 Summary: My laboratory is interested in the roles of lipid second messengers generated in the phosphatidylinositol (PI) cycle in phototransduction, retinal degeneration, and protection of retinal cells from apoptosis. One messenger, PI-3,4,5-P3, generated by the PI-3 kinase (PI3K), plays an important role in cell protection, cell proliferation, glucose homeostasis, membrane trafficking and cytoskeletal rearrangement. In neuronal cells, activation of PI3K has been shown to protect the cells from stress-induced apoptosis. However, the functions of PI3K in visual systems are not well understood. Retinal pigment epithelial (RPE) cells are post-mitotic cells that provide the "blood-retinal barrier", and control the flow of nutrients and waste products between the retina and the blood. Death of these cells leads to death of rod and cone photoreceptor cells, and compromise in RPE function may be a contributing factor in age-related macular degeneration. Since Bcl-x, a downstream target of PI3K is highly expressed in RPE cells under cytotoxic stress, it is likely that PI3K plays an important role in RPE cell survival. We hypothesize that PI3K and BOI-xL are major survivor factors in RPE. To test this hypothesis, we will use a genetic approach to disrupt PI3K and Bcl-x (BCl-xL) in RPE,

52

Macular Degeneration

and compare the functional, biochemical, and structural phenotypes of the mutant mice with those of wild type mice. Since the conventional PI3K(p85odp110o_) and Bcl-x knockout mice are neonatal or embryonic lethal, mouse models of PI3K and Bcl-x null mutation will be generated in a RPE specific fashion, using the Cre/Iox system. Therefore, I propose 1) to generate and characterize transgenic mice expressing RPEspecific Cre driven by RPE65 promoter; 2) to generate RPE-specific PI3K and/or Bcl-x null mice and test the hypothesis that PI3K and BCl-xL are involved in RPE cell survival, 3) to test the hypothesis that compromised RPE cells may exacerbate the death of photoreceptor cells with PI3K and/or Bcl-x null mutations using the RPEspecific PI3K, or Bcl-x null mice generated in this study and the ABCR null (RPE degeneration) mice. A major goal of this project in the context of the COBRE program is to establish mouse models that can be used in future studies to elucidate the mechanisms of inherent retinal degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROS MEMBRANE PROTEINS AND RETINAL DEGENERATIVE DISEASES Principal Investigator & Institution: Molday, Robert S.; Professor; University of British Columbia 2075 Wesbrook Pl Vancouver, Timing: Fiscal Year 2001; Project Start 01-APR-1978; Project End 31-AUG-2005 Summary: (Adapted from applicant's abstract): Rod and cone outer segments are unique compartments of photoreceptor cells where the process of phototransduction occurs. The overall goal of this research program is to identify and characterize outer segment membrane proteins and elucidate their role in i) the visual process, ii) outer segment morphogenesis, structure, and renewal, and iii) inherited retinal degenerative diseases. The specific aims of the current grant period are as follows: 1) To study the structural, functional, and regulatory properties of ABCR, the photoreceptor ATP binding cassette (ABC) transporter of photoreceptors, and determine its cellular and subcellular distribution in rod and cone photoreceptors. 2) To develop a heterologous cell (COS-1) system to express wild-type and mutant forms of ABCR for structure-function analyses. This system will be used to determine how missense mutations in ABCR implicated in Stargardt disease alter the structure of ABCR and its possible function as a transporter. 3) To identify, clone, characterize and localize novel low abundant rod outer segment membrane proteins as a first step in determining their role in outer segment structure, function and renewal and their possible involvement in inherited retinal degenerative diseases. For these studies, a variety of current biochemical, molecular biology, cell biology and biophysical methods will be employed along with a unique panel of highly specific monoclonal antibodies and cDNAs to ABCR and novel, undefined outer segment proteins. The results of these studies should lead to new information about the morphogenesis, structure and function of rod and cone outer segments and provide insight into the role of ABCR in the visual cycle and retinal degenerative diseases including Stargardt macular dystrophy and age-related macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RPE65 IN RETINAL METABOLISM AND DEGENERATION Principal Investigator & Institution: Thompson, Debra A.; Ophthalmology and Visual Sciences; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005

Studies

53

Summary: (Adapted from the applicant's abstract): The retinal pigment epithelium (RPE) plays a critical role in the maintenance of normal photoreceptor functions and has been implicated in several visual disorders, including macular degenerations and dystrophies. The investigator has cloned and characterized the first known RPE-specific human gene, RPE65, and has shown that mutations in this gene are responsible for certain forms of autosomal recessive childhood-onset severe retinal dystrophy (arCSRD), a finding supported by reports of RPE65 defects in Leber's congenital amaurosis. A research program has been developed to study the function of RPE65 in the normal biology of the retina and in the disease state, based on the view that RPE65 is necessary for the isomerase activity involved in the conversion of vitamin A to 11-cis retinal. Four specific aims have been identified for the proposed funding period. (1) Recombinant protein-protein interactions and enzyme activity will be studied in cultured cells transfected with RPE65 expression constructs in order to distinguish between the two prevailing hypotheses about the specific role of RPE65 in RPE retinoid metabolism. (2) Site-directed mutagenesis will be used with assays of expression and protein function to elucidate the role of RPE65 mutations in the pathogenesis of arCSRD to test the hypothesis that disease-associated mutations in RPE65 result in functional null alleles that disrupt the 11-cis retinal biosynthetic pathway. This aim will include further characterization of mutations present in patient populations. (3) Because preliminary information indicates that RPE65 is down-regulated by a variety of factors that are known to be related to aging and disease processes, and because decreased levels of RPE65 are implicated in retinal degeneration, the mechanisms involved in this down-regulation will be investigated, as well as the effects of aging and other physiological conditions on RPE65 expression. (4) Effects of the RPE65 mutation in a large animal model of arCSRD will be characterized in assays of the biochemistry and enzymology of retinoid metabolism, to test the hypothesis that defects resulting from RPE65 mutations will be amenable to retinal replacement therapy. The long-term goals of this project are to elucidate the mechanisms by which RPE65 defects contribute to retinal degeneration, and to lay the groundwork for the development of therapeutic approaches to the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RUNX SPECIFIC ANGIOGENESIS INHIBITORS Principal Investigator & Institution: Passaniti, Antonino; Pathology; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: (provided by applicant): Recruitment of new blood vessels (angiogenesis) is required for tumor growth and metastasis. Therefore, the development of angiogenesis inhibitors represents a new approach that may increase the effectiveness of existing cancer treatments. Runt family genes (Runx1,2,3) are transcription factors that playa key role in vascular development including endothelial cell (EC) migration and stem cell recruitment to promote angiogenesis. Runx DNA binding is enhanced by association with the product of the Cbf gene which forms a trimeric DNA binding complex whose 3-dimensional (3D) structure has recently been determined. Computer-aided rational drug design (CADD) can be used to identify chemical compounds with the potential to become therapeutic agents. CADD database searching involves screening of a 3D chemical database to select small molecules that "fit" in the binding site of interest on the target biomolecule. The identified small molecules are then obtained and subjected to experimental assays to select those with the appropriate biological activity. Use of a database of commercially available compounds avoids the need for chemical synthesis,

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Macular Degeneration

thereby facilitating the identification of active compounds. Our hypothesis is that specific inhibition of Runx-mediated transcriptional activation will inhibit EC migration and angiogenesis. Our goals are to use CADD, in combination with the available 3D structure of Runt to identify compounds with a high potential to bind selectively to Runt. Both the DNA and Cbf binding regions of Runt will be individually targeted. The selected compounds will be obtained and subjected to experimental testing using assays to identify compounds with the desired Runt-binding activities to verify that they are Runt-specific antagonists. An EC migration assay will then be used to screen candidate compounds for biological activity. These approaches are one of the first attempts to inhibit angiogenesis via transcriptional targeting. Since inhibiting Runx transcriptional activity should reduce angiogenesis, the growth of both hematopoietic and solid tumors that depend on a blood supply for survival and growth will be inhibited. The lead compounds developed from this application could also find utility in non-cancer situations, such as macular degeneration, atherosclerosis, or diabetic retinopathy, where uncontrolled angiogenesis is responsible for the pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIBLING STUDY OF AGE-RELATED MACULAR DEGENERATION Principal Investigator & Institution: Dryja, Thaddeus P.; Professor; Massachusetts Eye and Ear Infirmary 243 Charles St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): We propose to recruit pairs of siblings for a molecular genetic search for genes having a role in the development of neovascular agerelated macular degeneration (AMD). Two types of sibling pairs will be recruited, extremely discordant sibpairs and extremely concordant sibpairs. Extremely discordant sibpairs will be composed of one member, the index sib, with neovascular AMD, and the second member with few or no aging signs of the macula at the age at which the index sibling developed neovascular AMD. Extremely concordant sibpairs will be composed of two siblings with neovascular AMD. Leukocyte DNA will be purified from blood samples collected from these siblings. The sibpairs will form the basis for a genome-wide linkage study to search for chromosomal regions where the extremely discordant pairs, on average, share fewer alleles than expected by chance alone, and where the extremely concordant sibpairs, on average, share more alleles than expected. Chromosomal regions having these properties are likely to harbor AMD genes. In addition, candidate genes that may have a role in susceptibility to AMD, such as ABCA4 and apoE, will be analyzed by evaluating DNA sequence variations in those genes and looking for a correlation between any alleles and neovascular AMD. To our knowledge, a molecular genetics approach to finding genes for neovascular AMD based on extremely discordant and extremely concordant sibpairs has not been previously carried out by any other group of investigators. If successful, our work should provide substantial progress toward identifying the genetic causes of neovascular AMD, one of the leading causes of legal blindness among the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUBCONJUNCTIVAL ROUTE TO PROLONG CORTICOSTEROID DELIVERY Principal Investigator & Institution: Kompella, Uday B.; Associate Professor; Pharmaceutical Sciences; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2006

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55

Summary: (provided by applicant): This study proposes subconjunctivally injectable biodegradable nano- and micro-particles to sustain the delivery of budesonide, a corticosteroid, to the posterior segment of the eye for a few months. The concept of continuous delivery of ultra-low amounts of budesonide to the posterior segment of the eye will significantly advance the therapy of disorders associated with difficult to reach tissues such as choroid, retina, and vitreous. Budesonide, a very potent corticosteroid with high local activity, low systemic activity, and vascular endothelial growth factor (VEGF)-inhibitory activity, is likely to find application in treating multiple inflammatory, proliferative, and neovascular disorders of the eye. The proposed study will enable the PI to begin establishing his research with this promising new therapeutic agent for ocular therapies. In this study, budesonide particles will be prepared using poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer that has been used in surgical sutures for over 30 years. The proposed research on subconjunctival budesonide-PLGA particles for prolonged budesonide delivery is likely to advance the delivery of other therapeutic agents targeted to the posterior segment. The objective of this study is to test the hypothesis that subconjunctival injection of budesonide-PLGA particles will sustain budesonide delivery to the posterior segment for up to 4 months. The specific aims of this study are: (1) To prepare and characterize biodegradable particles capable of releasing budesonide for about four months. (2) To determine whether the tissue budesonide levels increase with increasing subconjunctival dose of budesonide-PLGA(poly(lactic-co-glycolic acid) particles, without inducing lens opacities or ocular hypertension. This study entails fabrication of budesonide-PLGA particles and in vivo drug delivery studies. The proposed budesonide-delivery system is likely to benefit several disorders of the eye including proliferative vitreoretinopathy, cystoid macular edema, macular degeneration, uveitis, sarcoidosis, and scleritis. Based on this study, the PI will submit an RO-l proposal to assess subconjunctival budesonide-PLGA particles for the therapy of posterior segment disorders associated with inflammation and/or VEGF elevation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SUPPLEMENTAL OXYGEN FOR HYPOXIA-RELATED RETINAL DESEASES Principal Investigator & Institution: Nguyen, Quan D.; Medicine; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2006 Summary: (Candidate's Abstract) Hypoxia is thought to play a role in the pathogenesis of several ocular diseases. It is Clear that hypoxia is the driving force behind the development of retinal neovascularization (NV) in patients with ischemic retinopathies, including diabetic retinopathy and central and branch retinal vein occlusions. Macular edema is another major cause of decreased vision in ischemic retinopathies and it is suspected, but not yet proven that hypoxia plays a critical role. Likewise, it is suspected, but not yet proven, that hypoxia contributes to the development of choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD). Supplemental inspired oxygen provides a means to enhance oxygenation in the retina and choroid. We propose to use supplemental inspired oxygen to test several hypotheses related to the role of hypoxia in ocular NV and macular edema. The following experimental questions will be addressed. (1) Does supplemental inspired oxygen cause regression or slow progression of retinal NV that is not high risk in patients with diabetic retinopathy? (2) Does supplemental oxygen cause improvement in macular edema in patients with ischemic retinopathy? (3) Does supplemental oxygen

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cause stabilization or improvement in AMD patients with predominantly occult subfoveal CNV? (4) Does supplemental oxygen decrease recurrent CNV in AMD patients with predominantly classic CNV treated with photodynamic therapy? The answers to these questions will provide important insights into the pathogenesis of retinal diseases that could lead to the development of new treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THERAPY DEGENERATIONS

FOR

DOMINANTLY

INHERITED

RETINAL

Principal Investigator & Institution: Duncan, Jacque L.; Ophthalmology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: Retinitis pigmentosa (RP) is a heterogeneous group of hereditary retinal degenerations (RDs) that affects 1 in 3,500 people worldwide. Age- related macular degeneration (AMD) affects as many as 1 in 4 people by the age of 75 and is the leading cause of blindness in people over age 50 in the US. There are currently no effective treatments to prevent photoreceptor degeneration and vision loss in patients with RP, or in most patients with AMD. Research efforts are being directed toward between understanding of the pathogenesis of these RDs and to develop therapies for them. The Sponsor's laboratory has recently demonstrated that subretinal injection of recombinant adeno-associated virus vectors for sustained injection of ribozymes in a rodent model of RP can delay photoreceptor loss and elevate a- and b-wave amplitudes in the ERG for at least 3 months. The relationship between rod and cone function with ribozymes, is largely unknown. The goals of the proposed experiments are to determine the duration of cone and rod photoreceptor survival and functional rescue by single and multiple administrations of ribozymes and to determine how late in the degenerative process ribozyme administration can rescue retinal function in S334ter and P23H rhodopsin mutant rat lines. These mutations in the rhodopsin gene are similar to those found in dominantly inherited human RP. We hypothesize that rescue of rod cell survival and function will also benefit cone cell survival and function. The proposed research and training plan provides enormous opportunities to help patients with both RP and AMD. The expertise the Candidate will gain using animal models of RD to develop and deliver therapies for RDs will be extremely valuable in her future career as an independent researcher. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: UNIFYING DEGENERATION

GENETICS

EPIDEMIOLOGY

OF

MACULAR

Principal Investigator & Institution: Pericak-Vance, Margaret A.; Professor; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 15-JUN-2000; Project End 31-MAY-2005 Summary: Age-related macular degeneration (AMD) is the most common cause of severe vision loss among individuals over age 50 in the U.S. The socioeconomic impact is considerable, and is expected to become greater as the U.S. population ages. Unfortunately, treatment options remain limited because the etiology of this devastating disease remains unknown. Considerable evidence implicates a combination of genetic, environmental, and biological factors in the pathogenesis of AMD as such suggested genetic effect involves the ATP-binding transporter (ABCR) gene. We thus hypothesize that underlying susceptibility gene(s) are critical to the development of AMD, and likely

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interact with environmental factors to trigger both the development and progression of the disease. The purpose of this study is to elucidate the genetic susceptibility to the development of AMD and to analyze the interaction of these genes with environmental influences. We will use both candidate gene and genomic screening approaches to identify these genes. Already identified genetic and environmental risk factors will be evaluated and current statistical methodologies will be adapted to examine the possible interactions. Multiplex (greater than 1 AMD affected/family) families will be recruited for the genetic analyses and detailed risk factor information will be collected on all study participants. Family-based association methods will be used to evaluate candidate genes, environmental risk factors and gene- gene and gene-environment interactions. The information derived from this study will further our understanding of this complex disease. The identification of specific susceptibility genes and evaluation of geneenvironment interaction will be crucial for future studies in unraveling the etiology of AMD and developing better treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VISUAL CYCLE IN HUMAN PHOTORECEPTOR AND RPE DISEASE Principal Investigator & Institution: Cideciyan, Artur V.; Ophthalmology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 05-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from applicant's abstract): Biochemical and physiological studies in vitro and in retina-specific ABC transporter (ABCR) -/- knockout mice suggest that ABCR accelerates recovery of rod photoreceptor resensitization after intense light exposure by transporting isomerized chromphore, all-trans-retinal, across the rod outer segment disk membrane. The current proposal is to test hypotheses about the role of ABCR in human disease as follows: (1) Study the visual cycle abnormalities in patients with retinopathy due to ABCR mutations with the goals of dissecting the contributions of primary rod effects vs. secondary disease consequences and learning the relationship between primary rod abnormalities and the genotype; (2) Investigate the basis of rod visual loss in these patients by testing the hypothesis that desensitization by equivalent light contributes to the visual loss, and determine if short term trial of unilateral light reduction can alter rod sensitivity and select mutations; (3) Test whether heterozygotes of ABCR mutations show visual cycle abnormalities and to approach from the visual function perspective the issue of ABCR sequence variance as risk factors in age related macular degeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISMS

VISUAL

DYSFUNCTION

AND

AGING--UNDERLYING

Principal Investigator & Institution: Owsley, Cynthia; Professor; Ophthalmology; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2001; Project Start 01-APR-1983; Project End 31-DEC-2005 Summary: (Adapted from Applicant's abstract): A ubiquitous problem of growing old is difficulty seeing at night and under low illumination. Poor vision under reduced light levels in the elderly hinders their performance of daily activities, and has been linked to the occurrence of motor vehicle collisions and falls, which result in injury and elevated mortality risk. Even for those older adults who are free of significant eye disease there can be scotopic dysfunction, suggesting that these impairments are due to a biological aging of the visual system. Optical changes in the aged eye cannot account for the

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severity of night/low luminance vision problems, suggesting that they have a neural origin. Older adults with early age-related macular degeneration (AMD) exhibit similar night/low luminance vision problems, but theirs are typically more severe. Our longterm goal is to identify the causes of scoptic deficits in older adults and in those with early AMD so that treatment interventions to minimize or reverse these deficits can be developed thus enhancing older adults' quality of life. Studies will focus on retinal mechanisms that may underlie these impairments. The specific aims of this research plan are: (1) to identify mechanisms of scotopic sensitivity impairment and dark adaptation delays in aging and early AMD using flash electroretinography and dark adaptometry; (2) to develop a questionnaire instrument for measuring health-related quality of life that is targeted at nighttime/low luminance vision problems; and (3) to evaluate the impact of vitamin A in reversing or minimizing scotopic sensitivity and delays in dark adaptation and in enhancing vision-targeted health-related quality of life in aging and early AMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: VISUAL IMPAIRMENT, TREATMENT, AND EFFECTS ON THE ELDERLY Principal Investigator & Institution: Sloan, Frank A.; J. Alexander Mcmahon Professor; Ctr/Hlth Policy Law & Mgmt; Duke University Durham, Nc 27706 Timing: Fiscal Year 2001; Project Start 15-APR-2001; Project End 31-MAR-2005 Summary: This four-year study has four major objectives. (1) For elderly persons with diabetes mellitus diabetic retinopathy, glaucoma, and macular degeneration -- diseases that can cause serious impairments to vision and blindness -- we will analyze determinants of utilization of eye care services, and whether or not Medicare beneficiaries with diabetes/diabetic retinopathy and glaucoma receive care in accordance with minimal process of eye care standards. Such standards have been disseminated as guidelines by professional organizations. In this phase, we will address these issues. How do data on patient self-report of diagnosis compare with those obtained from physicians' diagnoses? What proportions of persons with the study diseases receive care at least at the minimum level of guidelines? Holding many factors constant, are there racial differences in treatments for these diseases? (2) We will study the longitudinal course of these diseases, measured in terms of visual and general functional status -- physical, cognitive -- and in terms of placement in a nursing home, and survival. We will analyze effects of care on changes in vision and the other outcome measures. Our data are unique both in terms of the length of time over which patients are followed and in the range of health outcome monitored. (3) We will assess the impact of diabetes, glaucoma, and macular degeneration on total Medicare and Medicaid program cost and on costs privately incurred. Program cost will include cost of vision and non-vision services. In our framework, program cost and patient adherence to guidelines will be jointly determined. (4) We will replicate the analysis of the first 2 objectives for complications of diabetes other than for eyes. We will also specify and estimate a dynamic model of utilization of Medicare-covered services by persons with diabetes -- both vision and nonvision care. The main database will be the National Long-Term Care Survey (NLTCS) for 1982-2001, merged with Medicare claims data for 1982-2001. Eleven papers are planned. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “macular degeneration” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for macular degeneration in the PubMed Central database: •

Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia Leventinese and age-related macular degeneration. by Marmorstein LY, Munier FL, Arsenijevic Y, Schorderet DF, McLaughlin PJ, Chung D, Traboulsi E, Marmorstein AD.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130587

•

Autologous transplantation of genetically modified iris pigment epithelial cells: A promising concept for the treatment of age-related macular degeneration and other disorders of the eye. by Semkova I, Kreppel F, Welsandt G, Luther T, Kozlowski J, Janicki H, Kochanek S, Schraermeyer U.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130591

•

Bestrophin, the product of the Best vitelliform macular dystrophy gene (VMD2), localizes to the basolateral plasma membrane of the retinal pigment epithelium. by Marmorstein AD, Marmorstein LY, Rayborn M, Wang X, Hollyfield JG, Petrukhin K.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18837

•

Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCRmediated retinal and macular degeneration. by Mata NL, Weng J, Travis GH.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16515

•

Drusen proteome analysis: An approach to the etiology of age-related macular degeneration. by Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME, Salomon RG, Hollyfield JG.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137479

•

Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration. by Bora PS, Hu Z, Tezel TH, Sohn JH, Kang SG, Cruz JM, Bora NS, Garen A, Kaplan HJ.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151400

•

New insights and new approaches toward the study of age-related macular degeneration. by Bok D.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137466

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

Risk of macular degeneration in users of statins: cross sectional study. by Hall NF, Gale CR, Syddall H, Phillips DI, Martyn CN.; 2001 Aug 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37398

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The Alzheimer's A[beta]-peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration. by Johnson LV, Leitner WP, Rivest AJ, Staples MK, Radeke MJ, Anderson DH.; 2002 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129354

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The vitelliform macular dystrophy protein defines a new family of chloride channels. by Sun H, Tsunenari T, Yau KW, Nathans J.; 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122639

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Therapy for macular degeneration: Insights from acne. by Sparrow JR.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153554

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Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. by Radu RA, Mata NL, Nusinowitz S, Liu X, Sieving PA, Travis GH.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153626

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Vitamin E supplementation and macular degeneration: randomised controlled trial. by Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ.; 2002 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116664

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with macular degeneration, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “macular degeneration” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for macular degeneration (hyperlinks lead to article summaries): •

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A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions. Author(s): Seddon JM, Santangelo SL, Book K, Chong S, Cote J. Source: American Journal of Human Genetics. 2003 October; 73(4): 780-90. Epub 2003 August 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12945014&dopt=Abstract

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A pilot study of ICG-guided laser photocoagulation for occult choroidal neovascularization presenting as a focal spot in age-related macular degeneration. Author(s): Da Pozzo S, Parodi MB, Ravalico G. Source: International Ophthalmology. 2001; 24(4): 187-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678394&dopt=Abstract

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A randomized clinical trial of a single dose of intravitreal triamcinolone acetonide for neovascular age-related macular degeneration: one-year results. Author(s): Gillies MC, Simpson JM, Luo W, Penfold P, Hunyor AB, Chua W, Mitchell P, Billson F. Source: Archives of Ophthalmology. 2003 May; 121(5): 667-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742844&dopt=Abstract

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Activated microglia in human retinitis pigmentosa, late-onset retinal degeneration, and age-related macular degeneration. Author(s): Gupta N, Brown KE, Milam AH. Source: Experimental Eye Research. 2003 April; 76(4): 463-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634111&dopt=Abstract

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Adult vitelliform macular degeneration: a clinicopathological study. Author(s): Arnold JJ, Sarks JP, Killingsworth MC, Kettle EK, Sarks SH. Source: Eye (London, England). 2003 August; 17(6): 717-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12928683&dopt=Abstract

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Advanced glycation end products in age-related macular degeneration. Author(s): Ishibashi T, Murata T, Hangai M, Nagai R, Horiuchi S, Lopez PF, Hinton DR, Ryan SJ. Source: Archives of Ophthalmology. 1998 December; 116(12): 1629-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869793&dopt=Abstract

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Age related macular degeneration: macular relocation surgery was not taken into account. Author(s): Wong D, Charteris DG, da Cruz L. Source: Bmj (Clinical Research Ed.). 2003 June 28; 326(7404): 1459; Author Reply 1459-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829574&dopt=Abstract

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Age related macular degeneration: smoking entails major risk of blindness. Author(s): Kelly SP, Edwards R, Elton P, Mitchell P. Source: Bmj (Clinical Research Ed.). 2003 June 28; 326(7404): 1458-9; Author Reply 145960. Erratum In: Bmj. 2003 August 9; 327(7410): 325. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12829572&dopt=Abstract

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Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Author(s): Bartlett H, Eperjesi F. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2003 September; 23(5): 383-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950886&dopt=Abstract

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Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies. Author(s): Ambati J, Ambati BK, Yoo SH, Ianchulev S, Adamis AP. Source: Survey of Ophthalmology. 2003 May-June; 48(3): 257-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12745003&dopt=Abstract

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Age-related macular degeneration: review of pathogenesis. Author(s): Zarbin MA. Source: Eur J Ophthalmol. 1998 October-December; 8(4): 199-206. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891890&dopt=Abstract

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Age-related macular degeneration--a genome scan in extended families. Author(s): Majewski J, Schultz DW, Weleber RG, Schain MB, Edwards AO, Matise TC, Acott TS, Ott J, Klein ML. Source: American Journal of Human Genetics. 2003 September; 73(3): 540-50. Epub 2003 July 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12900797&dopt=Abstract

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Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration. Author(s): Stone EM, Webster AR, Vandenburgh K, Streb LM, Hockey RR, Lotery AJ, Sheffield VC. Source: Nature Genetics. 1998 December; 20(4): 328-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843201&dopt=Abstract

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Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas. Author(s): Dentchev T, Milam AH, Lee VM, Trojanowski JQ, Dunaief JL. Source: Molecular Vision [electronic Resource]. 2003 May 14; 9: 184-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764254&dopt=Abstract

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Anecortave acetate as monotherapy for the treatment of subfoveal lesions in patients with exudative age-related macular degeneration (AMD): interim (month 6) analysis of clinical safety and efficacy. Author(s): D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger S, Luna S, Robertson SM, Russell S, Singerman L, Slakter JS, Sullivan EK, Yannuzzi L, Zilliox P; Anecortave Acetate Clinical Study Group. Source: Retina (Philadelphia, Pa.). 2003 February; 23(1): 14-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652226&dopt=Abstract

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Angiographic characteristics in patients undergoing macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): Kent DL, Fujii GY, Pieramici DJ, Reynolds SM, Melia M, Rossi JV, Humayun MS, Caffey S, De Juan E. Source: Retina (Philadelphia, Pa.). 2003 April; 23(2): 152-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707592&dopt=Abstract

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Anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration: promises and pitfalls. Author(s): Csaky K. Source: Ophthalmology. 2003 May; 110(5): 879-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750083&dopt=Abstract

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Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Author(s): Eyetech Study Group. Source: Ophthalmology. 2003 May; 110(5): 979-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750101&dopt=Abstract

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Autologous retinal pigment epithelium and choroid translocation in patients with exudative age-related macular degeneration: short-term follow-up. Author(s): van Meurs JC, Van Den Biesen PR. Source: American Journal of Ophthalmology. 2003 October; 136(4): 688-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516809&dopt=Abstract

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Autosomal dominant macular degeneration associated with 208delG mutation in the FSCN2 gene. Author(s): Wada Y, Abe T, Itabashi T, Sato H, Kawamura M, Tamai M. Source: Archives of Ophthalmology. 2003 November; 121(11): 1613-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609921&dopt=Abstract

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Benefit of coloured lenses for age-related macular degeneration. Author(s): Wolffsohn JS, Dinardo C, Vingrys AJ. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2002 July; 22(4): 300-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162481&dopt=Abstract

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Bilateral macular drusen in age-related macular degeneration. Prognosis and risk factors. Author(s): Holz FG, Wolfensberger TJ, Piguet B, Gross-Jendroska M, Wells JA, Minassian DC, Chisholm IH, Bird AC. Source: Ophthalmology. 1994 September; 101(9): 1522-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8090455&dopt=Abstract

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Binocular contrast inhibition in subjects with age-related macular degeneration. Author(s): Valberg A, Fosse P. Source: J Opt Soc Am a Opt Image Sci Vis. 2002 January; 19(1): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11778728&dopt=Abstract

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Biochemical defects in retina-specific human ATP binding cassette transporter nucleotide binding domain 1 mutants associated with macular degeneration. Author(s): Suarez T, Biswas SB, Biswas EE. Source: The Journal of Biological Chemistry. 2002 June 14; 277(24): 21759-67. Epub 2002 March 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11919200&dopt=Abstract

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Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCRmediated retinal and macular degeneration. Author(s): Mata NL, Weng J, Travis GH. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 June 20; 97(13): 7154-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852960&dopt=Abstract

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Brachytherapy--optional treatment for choroidal neovascularization secondary to agerelated macular degeneration. Author(s): Saric B, Sikic J, Katusic D, Vukojevic N. Source: Coll Antropol. 2001; 25 Suppl: 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817022&dopt=Abstract

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By the way doctor. I'm 72 and was recently told that I am losing a bit of my sight because of macular degeneration. My doctor assured me that it was progressing very slowly, but also said there wasn't really anything to do about it. But I read that zinc or vitamins might help. Should I be taking them? Author(s): Lee TH. Source: Harvard Health Letter / from Harvard Medical School. 2002 February; 27(4): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869993&dopt=Abstract

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Case-control study of the risk factors for age related macular degeneration. FranceDMLA Study Group. Author(s): Chaine G, Hullo A, Sahel J, Soubrane G, Espinasse-Berrod MA, Schutz D, Bourguignon C, Harpey C, Brault Y, Coste M, Moccatti D, Bourgeois H. Source: The British Journal of Ophthalmology. 1998 September; 82(9): 996-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9893587&dopt=Abstract

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Cataract extraction and age-related macular degeneration: associations, diagnosis and management. Author(s): Velez G, Weiter JJ. Source: Seminars in Ophthalmology. 2002 September-December; 17(3-4): 187-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759849&dopt=Abstract

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Cataract surgery and quality of life in patients with age related macular degeneration. Author(s): Lundstrom M, Brege KG, Floren I, Lundh B, Stenevi U, Thorburn W. Source: The British Journal of Ophthalmology. 2002 December; 86(12): 1330-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12446358&dopt=Abstract

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Cataract surgery in patients with age-related macular degeneration: one-year outcomes. Author(s): Armbrecht AM, Findlay C, Aspinall PA, Hill AR, Dhillon B. Source: Journal of Cataract and Refractive Surgery. 2003 April; 29(4): 686-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12686235&dopt=Abstract

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Changes in blood antioxidants and several lipid peroxidation products in women with age-related macular degeneration. Author(s): Nowak M, Swietochowska E, Wielkoszynski T, Marek B, Karpe J, Gorski J, Glogowska-Szelag J, Kos-Kudla B, Ostrowska Z. Source: Eur J Ophthalmol. 2003 April; 13(3): 281-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12747649&dopt=Abstract

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Changes in fluorescein angiogram early after surgical removal of choroidal neovascularization in age-related macular degeneration. Author(s): Sawa M, Kamei M, Ohji M, Motokura M, Saito Y, Tano Y. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 January; 240(1): 12-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954774&dopt=Abstract

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Cigarette smoking as a risk factor for cataract and age-related macular degeneration: a review of the literature. Author(s): DeBlack SS. Source: Optometry. 2003 February; 74(2): 99-110. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585737&dopt=Abstract

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Clinical observations supporting a theoretical model of choriocapillaris blood flow in treatment of choroidal neovascularization associated with age-related macular degeneration. Author(s): Staurenghi G, Flower RW. Source: American Journal of Ophthalmology. 2002 June; 133(6): 801-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036672&dopt=Abstract

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Clinical studies to implement Rheopheresis for age-related macular degeneration guided by evidence-based-medicine. Author(s): Klingel R, Fassbender C, Fassbender T, Gohlen B. Source: Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis. 2003 August; 29(1): 71-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12877897&dopt=Abstract

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Clinicopathologic correlation in hemorrhagic age-related macular degeneration. Author(s): Reynders S, Lafaut BA, Aisenbrey S, Broecke CV, Lucke K, Walter P, Kirchhof B, Bartz-Schmidt KU. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 April; 240(4): 279-85. Epub 2002 March 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11981641&dopt=Abstract

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Clinicopathological correlation of choroidal neovascularization after external beam radiotherapy in age-related macular degeneration. Author(s): Aisenbrey S, Lafaut BA, Reynders S, Szurman P, Grisanti S, Vanden Broecke C, Walter P, Bartz-Schmidt KU. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2003 April; 241(4): 269-76. Epub 2003 March 22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719987&dopt=Abstract

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Clusterin is present in drusen in age-related macular degeneration. Author(s): Sakaguchi H, Miyagi M, Shadrach KG, Rayborn ME, Crabb JW, Hollyfield JG. Source: Experimental Eye Research. 2002 April; 74(4): 547-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076098&dopt=Abstract

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Color Doppler imaging of choroidal circulation in patients with asymmetric agerelated macular degeneration. Author(s): Uretmen O, Akkin C, Erakgun T, Killi R. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 March-April; 217(2): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592053&dopt=Abstract

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Color Doppler imaging of the retrobulbar circulation in age-related macular degeneration. Author(s): Hosal BM, Karakoc G, Gursel E, Camur M. Source: Eur J Ophthalmol. 1998 October-December; 8(4): 234-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9891895&dopt=Abstract

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Comment on “Mathematical morphology in computerized analysis of angiograms in age-related macular degeneration”. Author(s): Hutchinson TP. Source: Medical Physics. 2002 December; 29(12): 2960; Author Reply 2961. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12512734&dopt=Abstract

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Cone dysfunction in patients with late-onset cone dystrophy and age-related macular degeneration. Author(s): Ladewig M, Kraus H, Foerster MH, Kellner U. Source: Archives of Ophthalmology. 2003 November; 121(11): 1557-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609911&dopt=Abstract

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Could statins prevent age-related macular degeneration? Author(s): Hall NF, Martyn CN. Source: Expert Opinion on Pharmacotherapy. 2002 July; 3(7): 803-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12083981&dopt=Abstract

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Cultivation of retinal pigment epithelial cells from human choroidal neovascular membranes in age related macular degeneration. Author(s): Schlunck G, Martin G, Agostini HT, Camatta G, Hansen LL. Source: Experimental Eye Research. 2002 May; 74(5): 571-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076078&dopt=Abstract

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Current use of dietary supplementation in patients with age-related macular degeneration. Author(s): Chang CW, Chu G, Hinz BJ, Greve MD. Source: Can J Ophthalmol. 2003 February; 38(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608514&dopt=Abstract

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Cystoid macular degeneration in chronic central serous chorioretinopathy. Author(s): Iida T, Yannuzzi LA, Spaide RF, Borodoker N, Carvalho CA, Negrao S. Source: Retina (Philadelphia, Pa.). 2003 February; 23(1): 1-7; Quiz 137-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12652224&dopt=Abstract

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Dark adaptation in age-related macular degeneration: relationship to the fellow eye. Author(s): Haimovici R, Owens SL, Fitzke FW, Bird AC. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 February; 240(2): 90-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931085&dopt=Abstract

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Decreased visual acuity associated with cystoid macular edema in neovascular agerelated macular degeneration. Author(s): Ting TD, Oh M, Cox TA, Meyer CH, Toth CA. Source: Archives of Ophthalmology. 2002 June; 120(6): 731-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12049577&dopt=Abstract

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Depression, visual acuity, comorbidity, and disability associated with age-related macular degeneration. Author(s): Brody BL, Gamst AC, Williams RA, Smith AR, Lau PW, Dolnak D, Rapaport MH, Kaplan RM, Brown SI. Source: Ophthalmology. 2001 October; 108(10): 1893-900; Discussion 1900-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11581068&dopt=Abstract

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Detachment of subfoveal choroidal neovascularization in age-related macular degeneration. Author(s): Rumelt S, Kaiserman I, Rehany U, Ophir A, Pikkel J, Loewenstein A. Source: American Journal of Ophthalmology. 2002 December; 134(6): 822-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470749&dopt=Abstract

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Detection and segmentation of drusen deposits on human retina: potential in the diagnosis of age-related macular degeneration. Author(s): Rapantzikos K, Zervakis M, Balas K. Source: Medical Image Analysis. 2003 March; 7(1): 95-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467724&dopt=Abstract

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Detection of drusen in the fellow eye of Japanese patients with age-related macular degeneration using scanning laser ophthalmoscopy. Author(s): Ishiko S, Akiba J, Horikawa Y, Yoshida A. Source: Ophthalmology. 2002 November; 109(11): 2165-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414434&dopt=Abstract

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Development of a health education programme for elderly with age-related macular degeneration: a focus group study. Author(s): Dahlin-Ivanoff S, Klepp KI, Sjostrand J. Source: Patient Education and Counseling. 1998 May; 34(1): 63-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9697558&dopt=Abstract

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Development of an ADL instrument targeting elderly persons with age-related macular degeneration. Author(s): Dahlin-Ivanoff S, Sonn U, Svensson E. Source: Disability and Rehabilitation. 2001 January 20; 23(2): 69-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11214718&dopt=Abstract

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Development of exudative age-related macular degeneration after cataract surgery. Author(s): Pollack A, Marcovich A, Bukelman A, Zalish M, Oliver M. Source: Eye (London, England). 1997; 11 ( Pt 4): 523-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9425419&dopt=Abstract

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Dietary carotenoids and certain cancers, heart disease, and age-related macular degeneration: a review of recent research. Author(s): Cooper DA, Eldridge AL, Peters JC. Source: Nutrition Reviews. 1999 July; 57(7): 201-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10453174&dopt=Abstract

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Dietary fat and risk for advanced age-related macular degeneration. Author(s): Seddon JM, Rosner B, Sperduto RD, Yannuzzi L, Haller JA, Blair NP, Willett W. Source: Archives of Ophthalmology. 2001 August; 119(8): 1191-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483088&dopt=Abstract

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Dietary prevention of age-related macular degeneration. Author(s): Pratt S. Source: J Am Optom Assoc. 1999 January; 70(1): 39-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457680&dopt=Abstract

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Difference between ophthalmologists' and patients' perceptions of quality of life associated with age-related macular degeneration. Author(s): Brown GC, Brown MM, Sharma S. Source: Can J Ophthalmol. 2000 April; 35(3): 127-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812481&dopt=Abstract

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Do age-related macular degeneration and cardiovascular disease share common antecedents? Author(s): Snow KK, Seddon JM. Source: Ophthalmic Epidemiology. 1999 June; 6(2): 125-43. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10420212&dopt=Abstract

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Does coenzyme Q10 play a role in opposing oxidative stress in patients with agerelated macular degeneration? Author(s): Blasi MA, Bovina C, Carella G, Genova ML, Jansen AM, Lenaz G, Brancato R. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2001 January-February; 215(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11125270&dopt=Abstract

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Dosimetric advantages of enhanced dynamic wedge in small field irradiation for the treatment of macular degeneration. Author(s): Edlund T, Leavitt DD, Gibbs FA Jr. Source: Medical Dosimetry : Official Journal of the American Association of Medical Dosimetrists. 1999 Spring; 24(1): 21-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10100161&dopt=Abstract

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Drusen are Cold Spots for Proteolysis: Expression of Matrix Metalloproteinases and Their Tissue Inhibitor Proteins in Age-related Macular Degeneration. Author(s): Leu ST, Batni S, Radeke MJ, Johnson LV, Anderson DH, Clegg DO. Source: Experimental Eye Research. 2002 January; 74(1): 141-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878827&dopt=Abstract

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Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. Author(s): Mullins RF, Russell SR, Anderson DH, Hageman GS. Source: The Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology. 2000 May; 14(7): 835-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10783137&dopt=Abstract

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Drusen in age-related macular degeneration: pathogenesis, natural course, and laser photocoagulation-induced regression. Author(s): Abdelsalam A, Del Priore L, Zarbin MA. Source: Survey of Ophthalmology. 1999 July-August; 44(1): 1-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10466585&dopt=Abstract

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Drusen proteome analysis: an approach to the etiology of age-related macular degeneration. Author(s): Crabb JW, Miyagi M, Gu X, Shadrach K, West KA, Sakaguchi H, Kamei M, Hasan A, Yan L, Rayborn ME, Salomon RG, Hollyfield JG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 12; 99(23): 14682-7. Epub 2002 October 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391305&dopt=Abstract

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Early detection and treatment of neovascular age-related macular degeneration. Author(s): Bressler NM. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2002 March-April; 15(2): 142-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12002198&dopt=Abstract

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Early detection, diagnosis and management of choroidal neovascularization in agerelated macular degeneration: the role of ophthalmologists. Author(s): Sickenberg M. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2001 July-August; 215(4): 247-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399930&dopt=Abstract

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Effect of depression on vision function in age-related macular degeneration. Author(s): Rovner BW, Casten RJ, Tasman WS. Source: Archives of Ophthalmology. 2002 August; 120(8): 1041-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149057&dopt=Abstract

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Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Author(s): Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y, Ma C, Menchini U, Miller J, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Strong HA, Stur M, Su XY, Virgili G; Treatment of Age-related Macular Degeneration with Photodynamic Therapy study group; Verteporfin in Photodynamic Therapy study group. Source: American Journal of Ophthalmology. 2003 September; 136(3): 407-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12967792&dopt=Abstract

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Effect of unilateral exudative age-related macular degeneration on binocular visual function. Author(s): Quillen DA. Source: Archives of Ophthalmology. 2001 November; 119(11): 1725-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11709032&dopt=Abstract

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Effects of triamcinolone acetonide on microglial morphology and quantitative expression of MHC-II in exudative age-related macular degeneration. Author(s): Penfold PL, Wong JG, Gyory J, Billson FA. Source: Clinical & Experimental Ophthalmology. 2001 June; 29(3): 188-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11446466&dopt=Abstract

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Effects of verteporfin therapy on contrast on sensitivity: Results From the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation-TAP report No 4. Author(s): Rubin GS, Bressler NM; Treatment of Age-Related Macular Degeneration with Photodynamic therapy (TAP) study group. Source: Retina (Philadelphia, Pa.). 2002 October; 22(5): 536-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441717&dopt=Abstract

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Efficacy of iloprost in nonexudative, age-related macular degeneration. Author(s): Gerardino L, Santoliquido A, Flore R, Dal Lago A, Gaetani E, Gasbarrini A, Papaleo P, Abed A, Pola R. Source: Journal of the American Geriatrics Society. 2000 October; 48(10): 1350-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11037033&dopt=Abstract

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Electrophysiological changes after 360 degrees retinotomy and macular translocation for subfoveal choroidal neovascularisation in age related macular degeneration. Author(s): Luke C, Aisenbrey S, Luke M, Marzella G, Bartz-Schmidt KU, Walter P. Source: The British Journal of Ophthalmology. 2001 August; 85(8): 928-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11466247&dopt=Abstract

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Eligibility for treatment and angiographic features at the early stage of exudative age related macular degeneration. Author(s): Haddad WM, Coscas G, Soubrane G. Source: The British Journal of Ophthalmology. 2002 June; 86(6): 663-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034690&dopt=Abstract

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Evaluation of the G protein coupled receptor-75 (GPR75) in age related macular degeneration. Author(s): Sauer CG, White K, Stohr H, Grimm T, Hutchinson A, Bernstein PS, Lewis RA, Simonelli F, Pauleikhoff D, Allikmets R, Weber BH. Source: The British Journal of Ophthalmology. 2001 August; 85(8): 969-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11466257&dopt=Abstract

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Evolving pathophysiological paradigms for age related macular degeneration. Author(s): Ciulla TA. Source: The British Journal of Ophthalmology. 2001 May; 85(5): 510-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316702&dopt=Abstract

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Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration. Author(s): Honda M, Sakamoto T, Ishibashi T, Inomata H, Ueno H. Source: Gene Therapy. 2000 June; 7(11): 978-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10849558&dopt=Abstract

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Expression of matrix metalloproteinase-7 in choroidal neovascular membranes in agerelated macular degeneration. Author(s): Kadonosono K, Yazama F, Itoh N, Sawada H, Ohno S. Source: American Journal of Ophthalmology. 1999 September; 128(3): 382-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10511046&dopt=Abstract

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External beam irradiation of subfoveal choroidal neovascularization complicating age-related macular degeneration: one-year results of a prospective, double-masked, randomized clinical trial. Author(s): Marcus DM, Sheils W, Johnson MH, McIntosh SB, Leibach DB, Maguire A, Alexander J, Samy CN. Source: Archives of Ophthalmology. 2001 February; 119(2): 171-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176977&dopt=Abstract

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External beam radiation in patients suffering from exudative age-related macular degeneration. A matched-pairs study and 1-year clinical follow-up. Author(s): Krott R, Staar S, Muller RP, Bartz-Schmidt KU, Esser P, Heimann K. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1998 December; 236(12): 916-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9865622&dopt=Abstract

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External beam radiotherapy for subretinal neovascularization in age-related macular degeneration: is this treatment efficient? Author(s): Staar S, Krott R, Mueller RP, Bartz-Schmidt KU, Heimann K. Source: International Journal of Radiation Oncology, Biology, Physics. 1999 September 1; 45(2): 467-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487573&dopt=Abstract

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External beam radiotherapy in exudative age-related macular degeneration: a pooled analysis of phase I data. Author(s): Chakravarthy U, MacKenzie G. Source: The British Journal of Radiology. 2000 March; 73(867): 305-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10817048&dopt=Abstract

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Exudative macular degeneration and intravitreal triamcinolone. A pilot study. Author(s): Penfold PL, Gyory JF, Hunyor AB, Billson FA. Source: Australian and New Zealand Journal of Ophthalmology. 1995 November; 23(4): 293-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11980075&dopt=Abstract

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Exudative macular degeneration and intravitreal triamcinolone: 18 month follow up. Author(s): Challa JK, Gillies MC, Penfold PL, Gyory JF, Hunyor AB, Billson FA. Source: Australian and New Zealand Journal of Ophthalmology. 1998 November; 26(4): 277-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843254&dopt=Abstract

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Face recognition in age related macular degeneration: perceived disability, measured disability, and performance with a bioptic device. Author(s): Tejeria L, Harper RA, Artes PH, Dickinson CM. Source: The British Journal of Ophthalmology. 2002 September; 86(9): 1019-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12185131&dopt=Abstract

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Factors influencing visual acuity after photocoagulation for subfoveal choroidal neovascularization of exudative age-related macular degeneration. Author(s): Yuzawa M, Tamakoshi A, Ueha M, Kawakubo H, Nakajima M. Source: Ophthalmology. 1996 December; 103(12): 2037-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9003337&dopt=Abstract

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Features of age-related macular degeneration on optical coherence tomography. Author(s): Van Kerckhoven W, Lafaut B, Follens I, De Laey JJ. Source: Bull Soc Belge Ophtalmol. 2001; (281): 75-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702647&dopt=Abstract

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Feeder vessel photocoagulation of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): Shiraga F, Ojima Y, Matsuo T, Takasu I, Matsuo N. Source: Ophthalmology. 1998 April; 105(4): 662-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9544641&dopt=Abstract

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Findings on retinal topography and thickness mapping in age-related macular degeneration. Author(s): Gieser JP, Mori M, Blair NP, Shahidi M. Source: Retina (Philadelphia, Pa.). 2001; 21(4): 352-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11508882&dopt=Abstract

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Fixation patterns and reading rates in eyes with central scotomas from advanced atrophic age-related macular degeneration and Stargardt disease. Author(s): Sunness JS, Applegate CA, Haselwood D, Rubin GS. Source: Ophthalmology. 1996 September; 103(9): 1458-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8841306&dopt=Abstract

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Fluorescent pigments of the retinal pigment epithelium and age-related macular degeneration. Author(s): Ben-Shabat S, Parish CA, Hashimoto M, Liu J, Nakanishi K, Sparrow JR. Source: Bioorganic & Medicinal Chemistry Letters. 2001 June 18; 11(12): 1533-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11412975&dopt=Abstract

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Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration. Quantitative relationship between retinal morphology and function. Author(s): Falsini B, Serrao S, Fadda A, Iarossi G, Porrello G, Cocco F, Merendino E. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1999 March; 237(3): 193-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10090581&dopt=Abstract

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Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Author(s): Ben-Shabat S, Itagaki Y, Jockusch S, Sparrow JR, Turro NJ, Nakanishi K. Source: Angewandte Chemie (International Ed. in English). 2002 March 1; 41(5): 814-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491345&dopt=Abstract

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Foveal congenital hypertrophy of the retinal pigment epithelium in the setting of geographic atrophy from age-related macular degeneration. Author(s): Apte RS, Bressler NM. Source: American Journal of Ophthalmology. 2003 January; 135(1): 120-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12504720&dopt=Abstract

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Foveal translocation for exudative age related macular degeneration. Author(s): McLeod D. Source: The British Journal of Ophthalmology. 2000 April; 84(4): 344-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10729288&dopt=Abstract

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Foveal translocation surgery in age-related macular degeneration. Author(s): Cekic O, Ohji M, Hayashi A, Fujikado T, Tano Y. Source: Lancet. 1999 July 24; 354(9175): 340. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440341&dopt=Abstract

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Foveolar choroidal blood flow in age-related macular degeneration. Author(s): Grunwald JE, Hariprasad SM, DuPont J, Maguire MG, Fine SL, Brucker AJ, Maguire AM, Ho AC. Source: Investigative Ophthalmology & Visual Science. 1998 February; 39(2): 385-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9477998&dopt=Abstract

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Frequency doubling technology perimetry in age-related macular degeneration. Author(s): Sheu SJ, Chen YY, Chou LC, Wu TT, Cheng KK. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 September; 65(9): 435-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12433030&dopt=Abstract

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Functional analysis after auto iris pigment epithelial cell transplantation in patients with age-related macular degeneration. Author(s): Abe T, Yoshida M, Tomita H, Kano T, Nakagawa Y, Sato M, Wada Y, Fuse N, Yamada T, Tamai M. Source: The Tohoku Journal of Experimental Medicine. 1999 December; 189(4): 295-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10739165&dopt=Abstract

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Fundus autofluorescence and age-related macular degeneration. Author(s): Spaide RF. Source: Ophthalmology. 2003 February; 110(2): 392-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578786&dopt=Abstract

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Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Author(s): Holz FG, Bellman C, Staudt S, Schutt F, Volcker HE. Source: Investigative Ophthalmology & Visual Science. 2001 April; 42(5): 1051-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274085&dopt=Abstract

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Fundus autofluorescence in patients with age-related macular degeneration and high risk of visual loss. Author(s): Lois N, Owens SL, Coco R, Hopkins J, Fitzke FW, Bird AC. Source: American Journal of Ophthalmology. 2002 March; 133(3): 341-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860971&dopt=Abstract

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Further evidence for an association of ABCR alleles with age-related macular degeneration. The International ABCR Screening Consortium. Author(s): Allikmets R. Source: American Journal of Human Genetics. 2000 August; 67(2): 487-91. Epub 2000 July 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880298&dopt=Abstract

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Further pathophysiological insights into age related macular degeneration. Author(s): Lip PL, Lip GY. Source: The British Journal of Ophthalmology. 2001 August; 85(8): 1013. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11466264&dopt=Abstract

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Gaining insight into age-related macular degeneration. Author(s): Frock TL. Source: Journal of the American Academy of Nurse Practitioners. 2002 May; 14(5): 20713. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051144&dopt=Abstract

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Gamma knife treatment of subfoveal, classic neovascularization in age-related macular degeneration: a pilot study. Author(s): Haas A, Papaefthymiou G, Langmann G, Schrottner O, Feigl B, Leber KA, Hanselmayer R, Pendl G. Source: Journal of Neurosurgery. 2000 December; 93 Suppl 3: 172-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11143240&dopt=Abstract

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Gender, oestrogen, hormone replacement and age-related macular degeneration: results from the Blue Mountains Eye Study. Author(s): Smith W, Mitchell P, Wang JJ. Source: Australian and New Zealand Journal of Ophthalmology. 1997 May; 25 Suppl 1: S13-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9267614&dopt=Abstract

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Genetic association of apolipoprotein E with age-related macular degeneration. Author(s): Klaver CC, Kliffen M, van Duijn CM, Hofman A, Cruts M, Grobbee DE, van Broeckhoven C, de Jong PT. Source: American Journal of Human Genetics. 1998 July; 63(1): 200-6. Erratum In: Am J Hum Genet 1998 October; 63(4): 1252. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9634502&dopt=Abstract

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Genetic association of manganese superoxide dismutase with exudative age-related macular degeneration. Author(s): Kimura K, Isashiki Y, Sonoda S, Kakiuchi-Matsumoto T, Ohba N. Source: American Journal of Ophthalmology. 2000 December; 130(6): 769-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11124296&dopt=Abstract

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Genetic linkage of vitelliform macular degeneration (Best's disease) to chromosome 11q13. Author(s): Stone EM, Nichols BE, Streb LM, Kimura AE, Sheffield VC. Source: Nature Genetics. 1992 July; 1(4): 246-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1302019&dopt=Abstract

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Genetic susceptibility to age related macular degeneration. Author(s): Yates JR, Moore AT. Source: Journal of Medical Genetics. 2000 February; 37(2): 83-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10662806&dopt=Abstract

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Genetics of macular dystrophies and implications for age-related macular degeneration. Author(s): Klaver CC, Allikmets R. Source: Dev Ophthalmol. 2003; 37: 155-69. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12876836&dopt=Abstract

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Genotype-phenotype analysis of ABCR variants in macular degeneration probands and siblings. Author(s): Bernstein PS, Leppert M, Singh N, Dean M, Lewis RA, Lupski JR, Allikmets R, Seddon JM. Source: Investigative Ophthalmology & Visual Science. 2002 February; 43(2): 466-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818392&dopt=Abstract

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Giant neurosensory detachments associated with disciform lesions in neovascular age related macular degeneration. Author(s): Apte RS, Sung JU, DiBernardo C, Feuer-Greenberg E. Source: The British Journal of Ophthalmology. 2003 June; 87(6): 795-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770991&dopt=Abstract

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Ginkgo biloba extract for age-related macular degeneration. Author(s): Cochrane Database Syst Rev. 2001;(3):CD002030 Source: Cochrane Database Syst Rev. 2000; (2): Cd001775. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687007

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Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes. Author(s): Samiec PS, Drews-Botsch C, Flagg EW, Kurtz JC, Sternberg P Jr, Reed RL, Jones DP. Source: Free Radical Biology & Medicine. 1998 March 15; 24(5): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9586798&dopt=Abstract

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Grading of infrared confocal scanning laser tomography and video displays of digitized color slides in exudative age-related macular degeneration. Author(s): Miura M, Elsner AE, Beausencourt E, Kunze C, Hartnett ME, Lashkari K, Trempe CL. Source: Retina (Philadelphia, Pa.). 2002 June; 22(3): 300-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055463&dopt=Abstract

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Granulomatous reaction to Bruch's membrane in age-related macular degeneration. Author(s): Dastgheib K, Green WR. Source: Archives of Ophthalmology. 1994 June; 112(6): 813-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7516148&dopt=Abstract

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Grid laser treatment of occult choroidal neovascularization in age related macular degeneration. Author(s): Cardillo Piccolino F, Ghiglione D, Allegri P. Source: International Ophthalmology. 1993 April; 17(2): 77-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7691775&dopt=Abstract

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Growth factor localization in choroidal neovascular membranes of age-related macular degeneration. Author(s): Amin R, Puklin JE, Frank RN. Source: Investigative Ophthalmology & Visual Science. 1994 July; 35(8): 3178-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7519180&dopt=Abstract

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Growth factors in age-related macular degeneration. Author(s): Spraul CW, Lang GE, Grossniklaus HE, Lang GK. Source: Ophthalmic Research. 1999; 31(3): 243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10224509&dopt=Abstract

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Growth factors in age-related macular degeneration: pathogenic and therapeutic implications. Author(s): Frank RN. Source: Ophthalmic Research. 1997; 29(5): 341-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9323725&dopt=Abstract

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Growth rate of subretinal neovascularization in age-related macular degeneration. Author(s): Vander JF, Morgan CM, Schatz H. Source: Ophthalmology. 1989 September; 96(9): 1422-6; Discussion 1426-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2476701&dopt=Abstract

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Guidelines for using verteporfin (visudyne) in photodynamic therapy to treat choroidal neovascularization due to age-related macular degeneration and other causes. Author(s): Verteporfin Roundtable 2000 and 2001 Participants; Treatment of age-related macular degeneration with photodynamic therapy (TAP) study group principal investigators; Verteporfin in photodynamic therapy (VIP) study group principal investigators. Source: Retina (Philadelphia, Pa.). 2002 February; 22(1): 6-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11884872&dopt=Abstract

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Haptoglobin phenotype in age-related macular degeneration patients. Author(s): Seider N, Beiran I, Miller-Lotan R, Dori D, Karp J, Miller B, Levy AP. Source: American Journal of Ophthalmology. 2003 November; 136(5): 911-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597045&dopt=Abstract

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Health maintenance issues of the elderly. Vision: age-related macular degeneration. Author(s): Bressler SB. Source: Md Med J. 1989 February; 38(2): 135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2915618&dopt=Abstract

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Help for macular degeneration. Author(s): McDonald HR. Source: Health News. 1999 December 15; 5(15): 1-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633581&dopt=Abstract

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Hereditary hypotrichosis (Marie-Unna type) and juvenile macular degeneration (Stargardt's maculopathy). Author(s): Marren P, Wilson C, Dawber RP, Walshe MM. Source: Clinical and Experimental Dermatology. 1992 May; 17(3): 189-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1451298&dopt=Abstract

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Hereditary macular degeneration in three generations. Author(s): Johnston SS, Darragh J, Nevin NC. Source: The British Journal of Ophthalmology. 1973 August; 57(8): 578-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4743920&dopt=Abstract

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Hereditary macular degeneration--a population survey in the country of Vsterbotten, Sweden. Author(s): Nordstrom S. Source: Hereditas. 1974; 78(1): 41-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4448697&dopt=Abstract

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Hereditary vitelliform macular degeneration: variable fundus findings within a single pedigree. Author(s): Maloney WF, Robertson DM, Duboff SM. Source: Archives of Ophthalmology. 1977 June; 95(6): 979-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=869756&dopt=Abstract

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Heredity and age-related macular degeneration. Observations in monozygotic twins. Author(s): Klein ML, Mauldin WM, Stoumbos VD. Source: Archives of Ophthalmology. 1994 July; 112(7): 932-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8031273&dopt=Abstract

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High blood pressure in choroidal arteries as a possible pathogenetic mechanism in senile macular degeneration. Author(s): Bischoff PM, Flower RW. Source: American Journal of Ophthalmology. 1983 September; 96(3): 398-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6614118&dopt=Abstract

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High-dose supplements for age-related macular degeneration: did you leave out centrum? Author(s): Abramson DH, Abramson HS. Source: Archives of Ophthalmology. 2002 November; 120(11): 1602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427092&dopt=Abstract

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High-risk characteristics of fellow eyes of patients with unilateral neovascular agerelated macular degeneration. Author(s): Sandberg MA, Weiner A, Miller S, Gaudio AR. Source: Ophthalmology. 1998 March; 105(3): 441-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9499774&dopt=Abstract

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Histologic and morphometric analysis of the choroid, Bruch's membrane, and retinal pigment epithelium in postmortem eyes with age-related macular degeneration and histologic examination of surgically excised choroidal neovascular membranes. Author(s): Spraul CW, Lang GE, Grossniklaus HE, Lang GK. Source: Survey of Ophthalmology. 1999 October; 44 Suppl 1: S10-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10548114&dopt=Abstract

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Histologic features of the early stages of age-related macular degeneration. A statistical analysis. Author(s): van der Schaft TL, Mooy CM, de Bruijn WC, Oron FG, Mulder PG, de Jong PT. Source: Ophthalmology. 1992 February; 99(2): 278-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1553220&dopt=Abstract

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Histopathology of age-related macular degeneration. Author(s): Green WR. Source: Molecular Vision [electronic Resource]. 1999 November 3; 5: 27. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10562651&dopt=Abstract

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Hot spots after photodynamic therapy for choroidal neovascularization in age-related macular degeneration. Author(s): Battaglia Parodi M, Da Pozzo S. Source: Retina (Philadelphia, Pa.). 2002 October; 22(5): 671-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441743&dopt=Abstract

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Hot spots in age-related macular degeneration. Author(s): Da Pozzo S. Source: Ophthalmology. 2000 July; 107(7): 1212-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10889072&dopt=Abstract

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How big is the burden of visual loss caused by age related macular degeneration in the United Kingdom? Author(s): Owen CG, Fletcher AE, Donoghue M, Rudnicka AR. Source: The British Journal of Ophthalmology. 2003 March; 87(3): 312-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598445&dopt=Abstract

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Hyperacuity test to evaluate vision through dense cataracts; research preliminary to a clinical study. IV. Data on patients with macular degeneration and minimal media disorders obtained with and without a pseudo-nuclear cataract 6/60 (20/200) at the Aravind Eye Hospital, Madurai, India. Author(s): Singh S, Aravind S, Hirose H, Enoch JM, Azen SP. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 1996 February; 73(2): 125-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8927313&dopt=Abstract

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Hyperopia and neovascularization in age-related macular degeneration. Author(s): Sandberg MA, Tolentino MJ, Miller S, Berson EL, Gaudio AR. Source: Ophthalmology. 1993 July; 100(7): 1009-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7686644&dopt=Abstract

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Hypertension, cardiovascular disease, and age-related macular degeneration. AgeRelated Macular Degeneration Risk Factors Study Group. Author(s): Hyman L, Schachat AP, He Q, Leske MC. Source: Archives of Ophthalmology. 2000 March; 118(3): 351-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721957&dopt=Abstract

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Identification of lesion components that influence visual function in age related macular degeneration. Author(s): Hogg R, Curry E, Muldrew A, Winder J, Stevenson M, McClure M, Chakravarthy U. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 609-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714405&dopt=Abstract

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IFN-alpha antibodies in patients with age-related macular degeneration treated with recombinant human IFN-alpha2a. Author(s): Ross C, Engler CB, Sander B, Bendtzen K. Source: Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research. 2002 April; 22(4): 421-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034024&dopt=Abstract

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Iloprost for age-related macular degeneration: long-term efficacy evaluation. Author(s): Gaetani E, Flex A, Pola P, Pola R. Source: Journal of the American Geriatrics Society. 2002 April; 50(4): 780-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982690&dopt=Abstract

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Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration. Author(s): Bora PS, Hu Z, Tezel TH, Sohn JH, Kang SG, Cruz JM, Bora NS, Garen A, Kaplan HJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 March 4; 100(5): 2679-84. Epub 2003 February 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589025&dopt=Abstract

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Impact of graphical user interface screen features on computer task accuracy and speed in a cohort of patients with age-related macular degeneration. Author(s): Scott IU, Feuer WJ, Jacko JA. Source: American Journal of Ophthalmology. 2002 December; 134(6): 857-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470754&dopt=Abstract

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Impact of visual function on computer task accuracy and reaction time in a cohort of patients with age-related macular degeneration. Author(s): Cochrane Database Syst Rev. 2002;(2):CD000254 Source: American Journal of Ophthalmology. 2002 March; 133(3): 350-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12076389

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Incidence of exudative age-related macular degeneration among elderly Americans. Author(s): Javitt JC, Zhou Z, Maguire MG, Fine SL, Willke RJ. Source: Ophthalmology. 2003 August; 110(8): 1534-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12917168&dopt=Abstract

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Inferior limited macular translocation for subfoveal choroidal neovascularization secondary to age-related macular degeneration: 1-year visual outcome and recurrence report. Author(s): Fujii GY, de Juan E Jr, Pieramici DJ, Humayun MS, Phillips S, Reynolds SM, Melia M, Schachat AP. Source: American Journal of Ophthalmology. 2002 July; 134(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095810&dopt=Abstract

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Insulin-like growth factor-I and its receptor in neovascular age-related macular degeneration. Author(s): Lambooij AC, van Wely KH, Lindenbergh-Kortleve DJ, Kuijpers RW, Kliffen M, Mooy CM. Source: Investigative Ophthalmology & Visual Science. 2003 May; 44(5): 2192-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714661&dopt=Abstract

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Inter- and intra-observer variability in grading lesions of age-related maculopathy and macular degeneration. Author(s): Scholl HP, Peto T, Dandekar S, Bunce C, Xing W, Jenkins S, Bird AC. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2003 January; 241(1): 39-47. Epub 2002 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545291&dopt=Abstract

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Interaction of A2E with model membranes. Implications to the pathogenesis of agerelated macular degeneration. Author(s): De S, Sakmar TP. Source: The Journal of General Physiology. 2002 August; 120(2): 147-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149277&dopt=Abstract

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Intraocular hemorrhage after systemic thrombolytic therapy in a patient with exudative macular degeneration. Author(s): Djalilian AR, Cantrill HC, Samuelson TW. Source: Eur J Ophthalmol. 2003 January-February; 13(1): 96-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635684&dopt=Abstract

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Intraocular microablation of choroidal tissue by a 308 nm AIDA excimer laser for RPE-transplantation in patients with age-related macular degeneration. Author(s): Holz FG, Bindewald A, Schutt F, Specht H. Source: Biomed Tech (Berl). 2003 April; 48(4): 82-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749285&dopt=Abstract

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Intraoperative light toxicity: a possible explanation for the association between cataract surgery and age-related macular degeneration. Author(s): Libre PE. Source: American Journal of Ophthalmology. 2003 November; 136(5): 961. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14597070&dopt=Abstract

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Intravitreal triamcinolone acetonide for exudative age related macular degeneration. Author(s): Jonas JB, Kreissig I, Hugger P, Sauder G, Panda-Jonas S, Degenring R. Source: The British Journal of Ophthalmology. 2003 April; 87(4): 462-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12642311&dopt=Abstract

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Intravitreal triamcinolone in subfoveal recurrence of choroidal neovascularisation after laser treatment in macular degeneration. Author(s): Ranson NT, Danis RP, Ciulla TA, Pratt L. Source: The British Journal of Ophthalmology. 2002 May; 86(5): 527-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11973247&dopt=Abstract

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Introduction of photodynamic therapy for the treatment of neovascular age-related macular degeneration: tracking a moving target. Author(s): Foot B, Foy R, Chakravarthy U, Wormald R. Source: Eye (London, England). 2003 July; 17(5): 583-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12855963&dopt=Abstract

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Is age-related macular degeneration associated with serum lipoprotein and lipoparticle levels? Author(s): Abalain JH, Carre JL, Leglise D, Robinet A, Legall F, Meskar A, Floch HH, Colin J. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 December; 326(1-2): 97-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417100&dopt=Abstract

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Is Chlamydia pneumoniae infection a risk factor for age related macular degeneration? Author(s): Ishida O, Oku H, Ikeda T, Nishimura M, Kawagoe K, Nakamura K. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 523-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714382&dopt=Abstract

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Is there an association between cataract surgery and age-related macular degeneration? Data from three population-based studies. Author(s): Freeman EE, Munoz B, West SK, Tielsch JM, Schein OD. Source: American Journal of Ophthalmology. 2003 June; 135(6): 849-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788126&dopt=Abstract

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JAMA patient page. Age-related macular degeneration. Author(s): Parmet S, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. 2002 November 13; 288(18): 2358. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12448423&dopt=Abstract

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Just the berries. Age-related macular degeneration. Author(s): Hamilton JR. Source: Can Fam Physician. 2000 December; 46(12): 2398-9. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11153406&dopt=Abstract

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Knowledge about cataract, glaucoma, and age related macular degeneration in the Hong Kong Chinese population. Author(s): Lau JT, Lee V, Fan D, Lau M, Michon J. Source: The British Journal of Ophthalmology. 2002 October; 86(10): 1080-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234882&dopt=Abstract

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Krypton laser in the management of disciform macular degeneration. Author(s): Talbot JF, Bird AC. Source: Trans Ophthalmol Soc U K. 1980 September; 100(3): 423-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6946633&dopt=Abstract

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Krypton Laser photocoagulation for neovascular lesions of age-related macular degeneration. Author(s): Fine SL, Hawkins BS, Maguire MG. Source: Archives of Ophthalmology. 1991 May; 109(5): 614-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1709001&dopt=Abstract

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Krypton laser photocoagulation of the senile disciform macular degeneration. Author(s): Oosterhuis JA, Van Eijk AW. Source: Bull Soc Belge Ophtalmol. 1983; 206: 27-35. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6200166&dopt=Abstract

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Lack of an association of apolipoprotein E gene polymorphisms with familial agerelated macular degeneration. Author(s): Schultz DW, Klein ML, Humpert A, Majewski J, Schain M, Weleber RG, Ott J, Acott TS. Source: Archives of Ophthalmology. 2003 May; 121(5): 679-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742846&dopt=Abstract

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Lack of association of mutations of the bestrophin gene with age-related macular degeneration in non-familial Japanese patients. Author(s): Akimoto A, Akimoto M, Kuroiwa S, Kikuchi T, Yoshimura N. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2001 January; 239(1): 66-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11271465&dopt=Abstract

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Large-spot size transpupillary thermotherapy for the treatment of occult choroidal neovascularization associated with age-related macular degeneration. Author(s): Thach AB, Sipperley JO, Dugel PU, Sneed SR, Park DW, Cornelius J. Source: Archives of Ophthalmology. 2003 June; 121(6): 817-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796252&dopt=Abstract

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Laser photocoagulation of neovascular lesions in senile macular degeneration. Author(s): Striga M, Mandic Z, Ivekovic R. Source: Acta Med Croatica. 1997; 51(4-5): 203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9473799&dopt=Abstract

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Laser treatment in subjects with high-risk clinical features of age-related macular degeneration. Posterior pole appearance and retinal function. Author(s): Guymer RH, Gross-Jendroska M, Owens SL, Bird AC, Fitzke FW. Source: Archives of Ophthalmology. 1997 May; 115(5): 595-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9152126&dopt=Abstract

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Light exposure and the risk of age-related macular degeneration: the Pathologies Oculaires Liees a l'Age (POLA) study. Author(s): Delcourt C, Carriere I, Ponton-Sanchez A, Fourrey S, Lacroux A, Papoz L; POLA Study Group. Source: Archives of Ophthalmology. 2001 October; 119(10): 1463-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594945&dopt=Abstract

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Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): D'Amico DJ, Friberg TR. Source: American Journal of Ophthalmology. 2001 August; 132(2): 289-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491094&dopt=Abstract

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Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): Pieramici DJ, de Juna E Jr. Source: American Journal of Ophthalmology. 2001 July; 132(1): 139-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11460828&dopt=Abstract

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Limited inferior macular translocation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): Pieramici DJ, De Juan E Jr, Fujii GY, Reynolds SM, Melia M, Humayun MS, Schachat AP, Hartranft CD. Source: American Journal of Ophthalmology. 2000 October; 130(4): 419-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11024414&dopt=Abstract

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Limited macular translocation for subfoveal choroidal neovascularization in agerelated macular degeneration. Author(s): Chang AA, Tan W, Beaumont PE, Zeldovich A. Source: Clinical & Experimental Ophthalmology. 2003 April; 31(2): 103-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648041&dopt=Abstract

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Little effect of tissue plasminogen activator in subretinal surgery for acute hemorrhage in age-related macular degeneration. Author(s): Hesse L, Meitinger D, Schmidt J. Source: Ger J Ophthalmol. 1996 November; 5(6): 479-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9479539&dopt=Abstract

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Living with macular degeneration: creative strategies used by older women. Author(s): Moore LW. Source: J Ophthalmic Nurs Technol. 1999 September-October; 18(5): 200-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10847047&dopt=Abstract

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Long term results of radiotherapy for subfoveal choroidal neovascularisation in age related macular degeneration. Author(s): Mauget-Faysse M, Chiquet C, Milea D, Romestaing P, Gerard JP, Martin P, Koenig F. Source: The British Journal of Ophthalmology. 1999 August; 83(8): 923-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10413694&dopt=Abstract

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Long term warfarin associated with bilateral blindness in a patient with atrial fibrillation and macular degeneration. Author(s): Ung T, James M, Gray RH. Source: Heart (British Cardiac Society). 2003 September; 89(9): 985. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12923003&dopt=Abstract

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Long-term outcome after radiation therapy for subfoveal choroidal neovascularization associated with age-related macular degeneration. Author(s): Mandai M, Takahashi M, Miyamoto H, Hiroshiba N, Kimura H, Ogura Y, Honda Y, Sasai K. Source: Japanese Journal of Ophthalmology. 2000 September-October; 44(5): 530-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11033133&dopt=Abstract

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Low dose radiation for subfoveal choroidal neovascularization in age-related macular degeneration. A pilot study: radiotherapy for age-related macular degeneration. Author(s): Valmaggia C, Bischoff P, Ries G, Seelentag W, Niederberger H, Speiser P. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 1997; 93(4): 317-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9665289&dopt=Abstract

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Low vision rehabilitation in patients with age-related macular degeneration at a tertiary eye care centre in southern India. Author(s): Khan SA, Das T, Kumar SM, Nutheti R. Source: Clinical & Experimental Ophthalmology. 2002 December; 30(6): 404-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427230&dopt=Abstract

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Low-dose radiation therapy for age-related macular degeneration. Author(s): Postgens H, Bodanowitz S, Kroll P. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 1997 October; 235(10): 656-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9349951&dopt=Abstract

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Low-dose radiotherapy for macular degeneration. Author(s): Sagerman RH, Gorty SG. Source: Front Radiat Ther Oncol. 2001; 35: 67-78. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351955&dopt=Abstract

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Lutein and zeaxanthin status and risk of age-related macular degeneration. Author(s): Gale CR, Hall NF, Phillips DI, Martyn CN. Source: Investigative Ophthalmology & Visual Science. 2003 June; 44(6): 2461-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766044&dopt=Abstract

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Macular infarction after transpupillary thermotherapy for subfoveal choroidal neovascularization in age-related macular degeneration. Author(s): Benner JD, Ahuja RM, Butler JW. Source: American Journal of Ophthalmology. 2002 November; 134(5): 765-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429257&dopt=Abstract

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Macular translocation in nonexudative age-related macular degeneration. Author(s): Eckardt C, Eckardt U. Source: Retina (Philadelphia, Pa.). 2002 December; 22(6): 786-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476108&dopt=Abstract

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Macular translocation with 360 degree retinotomy for management of age-related macular degeneration with subfoveal choroidal neovascularization. Author(s): Pertile G, Claes C. Source: American Journal of Ophthalmology. 2002 October; 134(4): 560-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383813&dopt=Abstract

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Macular translocation with 360-degree retinotomy for management of age-related macular degeneration with subfoveal choroidal neovascularization. Author(s): Aisenbrey S, Bartz-Schmidt U. Source: American Journal of Ophthalmology. 2003 May; 135(5): 748-9; Author Reply 749. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12719108&dopt=Abstract

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Maculas affected by age-related macular degeneration contain increased chelatable iron in the retinal pigment epithelium and Bruch's membrane. Author(s): Hahn P, Milam AH, Dunaief JL. Source: Archives of Ophthalmology. 2003 August; 121(8): 1099-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12912686&dopt=Abstract

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Management of age related macular degeneration: still room for improvement. Author(s): Howe LJ. Source: The British Journal of Ophthalmology. 2003 March; 87(3): 375. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598473&dopt=Abstract

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Management of ocular torsion and diplopia after macular translocation for agerelated macular degeneration: prospective clinical study. Author(s): Freedman SF, Holgado S, Enyedi LB, Toth CA. Source: American Journal of Ophthalmology. 2003 October; 136(4): 640-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14516803&dopt=Abstract

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Mechanism of macular degeneration starts to appear. Author(s): Lawrence DM. Source: Lancet. 2002 October 26; 360(9342): 1307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12414213&dopt=Abstract

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Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study. Author(s): Feher J, Papale A, Mannino G, Gualdi L, Balacco Gabrieli C. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2003 September-October; 217(5): 351-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12913326&dopt=Abstract

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Monitoring retinal function during transpupillary thermotherapy for occult choroidal neovascularization in age-related macular degeneration. Author(s): Falsini B, Focosi F, Molle F, Manganelli C, Iarossi G, Fadda A, Dorin G, Mainster MA. Source: Investigative Ophthalmology & Visual Science. 2003 May; 44(5): 2133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714653&dopt=Abstract

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Morphometric analysis of the macula in eyes with disciform age-related macular degeneration. Author(s): Kim SY, Sadda S, Pearlman J, Humayun MS, de Juan E Jr, Melia BM, Green WR. Source: Retina (Philadelphia, Pa.). 2002 August; 22(4): 471-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172115&dopt=Abstract

92

Macular Degeneration

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Morphometric analysis of the macula in eyes with geographic atrophy due to agerelated macular degeneration. Author(s): Kim SY, Sadda S, Humayun MS, de Juan E Jr, Melia BM, Green WR. Source: Retina (Philadelphia, Pa.). 2002 August; 22(4): 464-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172114&dopt=Abstract

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Multicenter prospective, randomized, double-masked, placebo-controlled study of Rheopheresis to treat nonexudative age-related macular degeneration: interim analysis. Author(s): Pulido JS; Multicenter Investigation of Rheopheresis for AMD (MIRA-1) Study Group. Source: Trans Am Ophthalmol Soc. 2002; 100: 85-106; Discussion 106-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545682&dopt=Abstract

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Natural history of macular subretinal hemorrhage in age-related macular degeneration. Author(s): Scupola A, Coscas G, Soubrane G, Balestrazzi E. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 1999; 213(2): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9885385&dopt=Abstract

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Neovascular age-related macular degeneration and its relationship to antioxidant intake. Author(s): Snellen EL, Verbeek AL, Van Den Hoogen GW, Cruysberg JR, Hoyng CB. Source: Acta Ophthalmologica Scandinavica. 2002 August; 80(4): 368-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190777&dopt=Abstract

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Neovascular age-related macular degeneration: present and future treatment options. Author(s): Votruba M, Gregor Z. Source: Eye (London, England). 2001 June; 15(Pt 3): 424-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11450768&dopt=Abstract

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Neuroticism predicts depression and disability in age-related macular degeneration. Author(s): Rovner BW, Casten RJ. Source: Journal of the American Geriatrics Society. 2001 August; 49(8): 1097-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555073&dopt=Abstract

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New insights and new approaches toward the study of age-related macular degeneration. Author(s): Bok D. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 12; 99(23): 14619-21. Epub 2002 Nov 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419853&dopt=Abstract

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New surgical treatments for macular degeneration. Author(s): York J, Glaser B, Murphy R. Source: J Ophthalmic Nurs Technol. 2000 September-October; 19(5): 250-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933322&dopt=Abstract

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New treatments for age-related macular degeneration. Author(s): Mittra RA. Source: Minn Med. 2003 April; 86(4): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12797657&dopt=Abstract

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NICE recommends photodynamic therapy for certain patients with macular degeneration. Author(s): Mayor S. Source: Bmj (Clinical Research Ed.). 2003 September 27; 327(7417): 698. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512456&dopt=Abstract

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Nitric oxide and lipid peroxidation are increased and associated with decreased antioxidant enzyme activities in patients with age-related macular degeneration. Author(s): Evereklioglu C, Er H, Doganay S, Cekmen M, Turkoz Y, Otlu B, Ozerol E. Source: Documenta Ophthalmologica. Advances in Ophthalmology. 2003 March; 106(2): 129-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12678277&dopt=Abstract

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Novel mechanism for age-related macular degeneration: an equilibrium shift between the angiogenesis factors VEGF and PEDF. Author(s): Ohno-Matsui K, Morita I, Tombran-Tink J, Mrazek D, Onodera M, Uetama T, Hayano M, Murota SI, Mochizuki M. Source: Journal of Cellular Physiology. 2001 December; 189(3): 323-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748590&dopt=Abstract

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Ocular blood flow measurements and their importance in glaucoma and age-related macular degeneration. Author(s): Garzozi HJ, Shoham N, Chung HS, Kagemann L, Harris A. Source: Isr Med Assoc J. 2001 June; 3(6): 443-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11433640&dopt=Abstract

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Ocular perfusion and age-related macular degeneration. Author(s): Ciulla TA, Harris A, Martin BJ. Source: Acta Ophthalmologica Scandinavica. 2001 April; 79(2): 108-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284745&dopt=Abstract

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Macular Degeneration

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One year follow up of macular translocation with 360 degree retinotomy in patients with age related macular degeneration. Author(s): Abdel-Meguid A, Lappas A, Hartmann K, Auer F, Schrage N, Thumann G, Kirchhof B. Source: The British Journal of Ophthalmology. 2003 May; 87(5): 615-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12714406&dopt=Abstract

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Ophthalmic plaque radiotherapy for age-related macular degeneration associated with subretinal neovascularization. Author(s): Finger PT, Berson A, Ng T, Szechter A. Source: American Journal of Ophthalmology. 1999 February; 127(2): 170-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10030559&dopt=Abstract

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Optimizing treatment of choroidal neovascularization feeder vessels associated with age-related macular degeneration. Author(s): Flower RW. Source: American Journal of Ophthalmology. 2002 August; 134(2): 228-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140030&dopt=Abstract

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Optokinetic nystagmus in patients with central scotomas in age related macular degeneration. Author(s): Valmaggia C, Charlier J, Gottlob I. Source: The British Journal of Ophthalmology. 2001 February; 85(2): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159480&dopt=Abstract

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Oral and silent reading performance with macular degeneration. Author(s): Lovie-Kitchin JE, Bowers AR, Woods RL. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2000 September; 20(5): 360-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11045244&dopt=Abstract

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Oral fluorescein angiography in patients with choroidal neovascularization and macular degeneration. Author(s): Bartsch DU, Elmusharaf A, El-Bradey M, Freeman WR. Source: Ophthalmic Surgery, Lasers & Imaging : the Official Journal of the International Society for Imaging in the Eye. 2003 January-February; 34(1): 17-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12570000&dopt=Abstract

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Organization of the human IMPG2 gene and its evaluation as a candidate gene in age-related macular degeneration and other retinal degenerative disorders. Author(s): Kuehn MH, Stone EM, Hageman GS. Source: Investigative Ophthalmology & Visual Science. 2001 December; 42(13): 3123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726612&dopt=Abstract

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Oxidative stress-induced mitochondrial DNA damage in human retinal pigment epithelial cells: a possible mechanism for RPE aging and age-related macular degeneration. Author(s): Liang FQ, Godley BF. Source: Experimental Eye Research. 2003 April; 76(4): 397-403. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634104&dopt=Abstract

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Perifoveal laser treatment for subfoveal choroidal neovascularization in age-related macular degeneration. Author(s): Falcone P, Chaudhry NA, Grannum E. Source: Ophthalmic Surgery and Lasers. 1998 November; 29(11): 933-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9824867&dopt=Abstract

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Photodynamic therapy for neovascular age-related macular degeneration. Author(s): Wormald R, Evans J, Smeeth L, Henshaw K. Source: Cochrane Database Syst Rev. 2003; (2): Cd002030. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12804420&dopt=Abstract

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Photodynamic therapy increases the eligibility for feeder vessel treatment of choroidal neovascularization caused by age-related macular degeneration. Author(s): Piermarocchi S, Lo Giudice G, Sartore M, Friede F, Segato T, Pilotto E, Midena E. Source: American Journal of Ophthalmology. 2002 April; 133(4): 572-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931801&dopt=Abstract

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Pigment epithelium-derived factor is deficient in the vitreous of patients with choroidal neovascularization due to age-related macular degeneration. Author(s): Holekamp NM, Bouck N, Volpert O. Source: American Journal of Ophthalmology. 2002 August; 134(2): 220-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12140029&dopt=Abstract

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Preclinical and phase 1A clinical evaluation of an anti-VEGF pegylated aptamer (EYE001) for the treatment of exudative age-related macular degeneration. Author(s): Eyetech Study Group. Source: Retina (Philadelphia, Pa.). 2002 April; 22(2): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11927845&dopt=Abstract

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Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration. Author(s): Rodanant N, Friberg TR, Cheng L, Aurora A, Bartsch D, Toyoguchi M, Corbin PS, El-Bradey MH, Freeman WR. Source: American Journal of Ophthalmology. 2002 October; 134(4): 577-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12383815&dopt=Abstract

96

Macular Degeneration

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Presentation delay in patients affected with exudative age-related macular degeneration. Author(s): Haddad WM, Seres A, Coscas G, Soubrane G. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 January; 240(1): 31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954778&dopt=Abstract

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Prevention of age related macular degeneration. Author(s): Hall NF, Gale CR. Source: Bmj (Clinical Research Ed.). 2002 July 6; 325(7354): 1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098707&dopt=Abstract

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Progression of age-related macular degeneration: association with body mass index, waist circumference, and waist-hip ratio. Author(s): Seddon JM, Cote J, Davis N, Rosner B. Source: Archives of Ophthalmology. 2003 June; 121(6): 785-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796248&dopt=Abstract

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Proton therapy for exudative age-related macular degeneration: a randomized, shamcontrolled clinical trial. Author(s): Ciulla TA, Danis RP, Klein SB, Malinovsky VE, Soni PS, Pratt LM, Pugh NO, Morphis JG, Bloch C, Cameron J. Source: American Journal of Ophthalmology. 2002 December; 134(6): 905-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470761&dopt=Abstract

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Quality of life with macular degeneration: perceptions of patients, clinicians, and community members. Author(s): Stein JD, Brown MM, Brown GC, Hollands H, Sharma S. Source: The British Journal of Ophthalmology. 2003 January; 87(1): 8-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488253&dopt=Abstract

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Quality of life with visual acuity loss from diabetic retinopathy and age-related macular degeneration. Author(s): Brown MM, Brown GC, Sharma S, Landy J, Bakal J. Source: Archives of Ophthalmology. 2002 April; 120(4): 481-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934322&dopt=Abstract

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Quantifying changes in RPE and choroidal vasculature in eyes with age-related macular degeneration. Author(s): McLeod DS, Taomoto M, Otsuji T, Green WR, Sunness JS, Lutty GA. Source: Investigative Ophthalmology & Visual Science. 2002 June; 43(6): 1986-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12037009&dopt=Abstract

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Radiotherapy and the treatment of age-related macular degeneration. External beam radiation therapy is effective in the treatment of age-related macular degeneration. Author(s): Finger PT, Chakravarthy U, Augsburger JJ. Source: Archives of Ophthalmology. 1998 November; 116(11): 1507-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9823353&dopt=Abstract

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Radiotherapy for age-related macular degeneration. Author(s): Gibbs SJ, Bird AC, Owens S, Plowman PN. Source: Clin Oncol (R Coll Radiol). 1998; 10(6): 356-60. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9890535&dopt=Abstract

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Recent advances in the treatment of exudative age-related macular degeneration, including transpupillary thermotherapy. Author(s): Ciulla TA. Source: Acta Ophthalmologica Scandinavica. 2003 April; 81(2): 103-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752045&dopt=Abstract

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Relation between size at birth and risk of age-related macular degeneration. Author(s): Hall NF, Gale CR, Syddall H, Martyn CN, Phillips DI. Source: Investigative Ophthalmology & Visual Science. 2002 December; 43(12): 3641-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454030&dopt=Abstract

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Repeated intravitreal injections of triamcinolone acetonide as treatment of progressive exudative age-related macular degeneration. Author(s): Jonas JB, Kreissig I, Degenring R. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 October; 240(10): 873-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12530461&dopt=Abstract

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Replacing the Amsler grid: a new method for monitoring patients with age-related macular degeneration. Author(s): Loewenstein A, Malach R, Goldstein M, Leibovitch I, Barak A, Baruch E, Alster Y, Rafaeli O, Avni I, Yassur Y. Source: Ophthalmology. 2003 May; 110(5): 966-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12750099&dopt=Abstract

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Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Author(s): Bernstein PS, Zhao DY, Wintch SW, Ermakov IV, McClane RW, Gellermann W. Source: Ophthalmology. 2002 October; 109(10): 1780-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359594&dopt=Abstract

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Macular Degeneration

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Retinal hemorrhage after photodynamic therapy in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration. Author(s): Theodossiadis GP, Panagiotidis D, Georgalas IG, Moschos M, Theodossiadis PG. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2003 January; 241(1): 13-8. Epub 2002 December 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12545287&dopt=Abstract

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Retinal translocation and photodynamic therapy for age-related macular degeneration with classic choroidal neovascularization: a clinicopathologic case report. Author(s): Grossniklaus HE, Brooks HL Jr, Sippy BD, Liu P. Source: Retina (Philadelphia, Pa.). 2002 December; 22(6): 818-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476118&dopt=Abstract

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Risk of age-related macular degeneration in eyes with macular drusen or hyperpigmentation: the Blue Mountains Eye Study cohort. Author(s): Wang JJ, Foran S, Smith W, Mitchell P. Source: Archives of Ophthalmology. 2003 May; 121(5): 658-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742843&dopt=Abstract

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Scotoma size and reading speed in patients with subfoveal occult choroidal neovascularization in age-related macular degeneration. Author(s): Ergun E, Maar N, Radner W, Barbazetto I, Schmidt-Erfurth U, Stur M. Source: Ophthalmology. 2003 January; 110(1): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12511348&dopt=Abstract

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Self-management improves functioning for age-related macular degeneration patients. Author(s): Rollins G. Source: Rep Med Guidel Outcomes Res. 2003 January 10; 14(1): 9-10, 12. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762306&dopt=Abstract

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Self-management of age-related macular degeneration and quality of life: a randomized controlled trial. Author(s): Brody BL, Roch-Levecq AC, Gamst AC, Maclean K, Kaplan RM, Brown SI. Source: Archives of Ophthalmology. 2002 November; 120(11): 1477-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427060&dopt=Abstract

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Serological association between Chlamydia pneumoniae infection and age-related macular degeneration. Author(s): Kalayoglu MV, Galvan C, Mahdi OS, Byrne GI, Mansour S. Source: Archives of Ophthalmology. 2003 April; 121(4): 478-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12695244&dopt=Abstract

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Serum leptin concentrations are decreased and correlated with disease severity in agerelated macular degeneration: a preliminary study. Author(s): Evereklioglu C, Doganay S, Er H, Cekmen M, Ozerol E, Otlu B. Source: Eye (London, England). 2003 April; 17(3): 350-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724698&dopt=Abstract

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Side effects after radiotherapy of age-related macular degeneration with the Nijmegen technique. Author(s): Hoyng CB, Tromp AI, Meulendijks CF, Leys A, van der Maazen RW, Deutman AF, Vingerling JR. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 May; 240(5): 337-41. Epub 2002 March 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073055&dopt=Abstract

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Spontaneous suprachoroidal haemorrhage in a patient with age-related macular degeneration on excessive anticoagulation therapy. Author(s): Knox FA, Johnston PB. Source: Eye (London, England). 2002 September; 16(5): 669-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194098&dopt=Abstract

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Spontaneous suprachoroidal hemorrhage in age-related macular degeneration presenting as angle-closure glaucoma. Author(s): Alexandrakis G, Chaudhry NA, Liggett PE, Weitzman M. Source: Retina (Philadelphia, Pa.). 1998; 18(5): 485-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9801053&dopt=Abstract

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Status of therapies in development for the treatment of age-related macular degeneration. Author(s): Hunt DW, Margaron P. Source: Idrugs. 2003 May; 6(5): 464-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789601&dopt=Abstract

100 Macular Degeneration

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Sub-retinal neovascular membrane in exudative macular degeneration. Author(s): Harris S. Source: Clinical & Experimental Optometry : Journal of the Australian Optometrical Association. 2003 January; 86(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12568652&dopt=Abstract

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The burden of age-related macular degeneration: results of a cohort study in two French referral centres. Author(s): Bonastre J, Le Pen C, Soubrane G, Quentel G. Source: Pharmacoeconomics. 2003; 21(3): 181-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558468&dopt=Abstract

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The effect of a lower blood pressure on choroidal filling in age-related macular degeneration. Author(s): Gaudio AR, Sandberg MA. Source: Retina (Philadelphia, Pa.). 1998; 18(5): 439-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9801040&dopt=Abstract

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The effect of membrane differential filtration on the colloid osmotic pressure in patients with age-related macular degeneration: significance to visual function? Author(s): Luke C, Widder RA, Walter P, Brunner R, Kirchhof B, Borberg H. Source: Therap Apher Dial. 2003 April; 7(2): 263-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12918954&dopt=Abstract

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The effects of dorzolamide on choroidal and retinal perfusion in non-exudative age related macular degeneration. Author(s): Harris A, Ciulla TA, Pratt LM, Rechtman E, Kagemann L, Piper HC, Garzozi HJ. Source: The British Journal of Ophthalmology. 2003 June; 87(6): 753-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12770975&dopt=Abstract

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The genetics of age-related macular degeneration. Author(s): Conley YP, Gorin MB. Source: Medsurg Nursing : Official Journal of the Academy of Medical-Surgical Nurses. 2003 August; 12(4): 238-41, 259. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14515603&dopt=Abstract

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The short-wavelength mechanisms of Stiles in age-related macular degeneration. Author(s): Hubschman JP, Vola JL, Conrath J, Berros P, Hougrand F. Source: Vision Research. 1998 November; 38(21): 3433-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9893861&dopt=Abstract

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Therapy for macular degeneration: insights from acne. Author(s): Sparrow JR. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4353-4. Epub 2003 Apr 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682280&dopt=Abstract

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Transpupillary thermotherapy of predominantly occult choroidal neovascularization in age-related macular degeneration with 12 months follow-up. Author(s): Algvere PV, Libert C, Lindgarde G, Seregard S. Source: Acta Ophthalmologica Scandinavica. 2003 April; 81(2): 110-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12752047&dopt=Abstract

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Treatment of pigment epithelial detachments due to age-related macular degeneration with intra-ocular C3F8 injection. Author(s): Gross-Jendroska M, Flaxel CJ, Schwartz SD, Holz FG, Fitzke FW, Gabel VP, Bird AC. Source: Australian and New Zealand Journal of Ophthalmology. 1998 November; 26(4): 311-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9843259&dopt=Abstract

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Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. Author(s): Radu RA, Mata NL, Nusinowitz S, Liu X, Sieving PA, Travis GH. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 April 15; 100(8): 4742-7. Epub 2003 Apr 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12671074&dopt=Abstract

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Ultrastructural immunocytochemistry of subretinal neovascular membranes in agerelated macular degeneration. Author(s): Das A, Puklin JE, Frank RN, Zhang NL. Source: Ophthalmology. 1992 September; 99(9): 1368-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1407971&dopt=Abstract

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Ultrastructure of Bruch's membrane in senile macular degeneration. Author(s): Tarkkanen A, Vannas S. Source: Acta Ophthalmol (Copenh). 1967; 45(5): 694-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5630839&dopt=Abstract

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Understanding macular degeneration. Author(s): York J, Glaser B, Murphy R. Source: J Ophthalmic Nurs Technol. 2000 May-June; 19(3): 116-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11249240&dopt=Abstract

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Unusual visual evoked potentials in patients with age-related macular degeneration. Author(s): Walter P, Konigsfeld P, Soudavar F, Brunner R. Source: Ophthalmologica. Journal International D'ophtalmologie. International Journal of Ophthalmology. Zeitschrift Fur Augenheilkunde. 2000 September-October; 214(5): 312-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10965243&dopt=Abstract

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Update in retina: photodynamic therapy for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): Sharma S. Source: Can J Ophthalmol. 2001 February; 36(1): 7-10. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11227391&dopt=Abstract

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Urinary metabolic studies in hereditary macular degeneration. Author(s): Holmgren G, Nordstrom S, Thorburn W. Source: Acta Ophthalmol (Copenh). 1974; 52(2): 225-30. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4406782&dopt=Abstract

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Use of a macular buckle in the treatment of exudative age-related macular degeneration. Author(s): Peyman GA, Conway MD, Recasens MA, Peralta E, Kertes PJ, Greve MD, ElDessouky ES. Source: Ophthalmic Surgery and Lasers. 1999 September-October; 30(8): 619-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10507564&dopt=Abstract

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Use of a simulator with CT option in radiotherapy of macular degeneration. Author(s): Vinh-Hung V, Verellen D, Van de Steene J, Nys F, Bijdekerke P, Linthout N, Claassens CP, Storme G. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 June 1; 41(3): 721-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9635725&dopt=Abstract

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Use of radiation in the treatment of age-related macular degeneration. Author(s): Flaxel CJ. Source: Ophthalmology Clinics of North America. 2002 December; 15(4): 437-44, V. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12515075&dopt=Abstract

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Utility values and age-related macular degeneration. Author(s): Brown GC, Sharma S, Brown MM, Kistler J. Source: Archives of Ophthalmology. 2000 January; 118(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10636413&dopt=Abstract

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Variability in fluorescein angiography interpretation for photodynamic therapy in age-related macular degeneration. Author(s): Kaiser RS, Berger JW, Williams GA, Tolentino MJ, Maguire AM, Alexander J, Madjarov B, Margherio RM. Source: Retina (Philadelphia, Pa.). 2002 December; 22(6): 683-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476092&dopt=Abstract

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Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials--TAP Report no. 5. Author(s): Blumenkranz MS, Bressler NM, Bressler SB, Donati G, Fish GE, Haynes LA, Lewis H, Miller JW, Mones JM, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Schachat AP, Schmidt-Erfurth U, Sickenburg M, Singerman LJ, Slakter JS, Strong A, Vannier S; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Source: Archives of Ophthalmology. 2002 October; 120(10): 1307-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365909&dopt=Abstract

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Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration. Author(s): Jonas JB. Source: American Journal of Ophthalmology. 2002 June; 133(6): 857; Author Reply 857-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036694&dopt=Abstract

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Verteporfin therapy of subfoveal choroidal neovascularization in patients with agerelated macular degeneration: additional information regarding baseline lesion composition's impact on vision outcomes-TAP report No. 3. Author(s): Bressler NM, Arnold J, Benchaboune M, Blumenkranz MS, Fish GE, Gragoudas ES, Lewis H, Schmidt-Erfurth U, Slakter JS, Bressler SB, Manos K, Hao Y, Hayes L, Koester J, Reaves A, Strong HA; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group. Source: Archives of Ophthalmology. 2002 November; 120(11): 1443-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427056&dopt=Abstract

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Vision and mobility performance of subjects with age-related macular degeneration. Author(s): Hassan SE, Lovie-Kitchin JE, Woods RL. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 2002 November; 79(11): 697-707. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462538&dopt=Abstract

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Visual function index (VF-14) in exudative age-related macular degeneration of long duration. Author(s): Riusala A, Sarna S, Immonen I. Source: American Journal of Ophthalmology. 2003 February; 135(2): 206-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566025&dopt=Abstract

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Visual hallucinations and Charles Bonnet syndrome after photodynamic therapy for age related macular degeneration. Author(s): Cohen SY, Bulik A, Tadayoni R, Quentel G. Source: The British Journal of Ophthalmology. 2003 August; 87(8): 977-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881339&dopt=Abstract

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Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration. Author(s): Hart PM, Chakravarthy U, Mackenzie G, Chisholm IH, Bird AC, Stevenson MR, Owens SL, Hall V, Houston RF, McCulloch DW, Plowman N. Source: Archives of Ophthalmology. 2002 August; 120(8): 1029-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149056&dopt=Abstract

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Visual prognosis of second eyes in patients with unilateral late exudative age-related macular degeneration. Author(s): Pauleikhoff D, Radermacher M, Spital G, Muller C, Brumm G, Lommatzsch A, Bird AC. Source: Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2002 July; 240(7): 539-42. Epub 2002 June 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12136283&dopt=Abstract

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Vitamin E supplementation and macular degeneration: randomised controlled trial. Author(s): Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ. Source: Bmj (Clinical Research Ed.). 2002 July 6; 325(7354): 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098721&dopt=Abstract

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Well-defined subfoveal choroidal neovascular membranes in age-related macular degeneration. Author(s): Lopez PF, Lambert HM, Grossniklaus HE, Sternberg P Jr. Source: Ophthalmology. 1993 March; 100(3): 415-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7681555&dopt=Abstract

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Wet-type macular degeneration. Author(s): Thompson J, Daniels C. Source: Radiol Technol. 1998 September-October; 70(1): 85-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779511&dopt=Abstract

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What can we learn about age-related macular degeneration from other retinal diseases? Author(s): Zack DJ, Dean M, Molday RS, Nathans J, Redmond TM, Stone EM, Swaroop A, Valle D, Weber BH. Source: Molecular Vision [electronic Resource]. 1999 November 3; 5: 30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10562654&dopt=Abstract

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Who should receive oral supplement treatment for age-related macular degeneration? Author(s): McBee WL, Lindblad AS, Ferris FL 3rd. Source: Current Opinion in Ophthalmology. 2003 June; 14(3): 159-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777936&dopt=Abstract

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X-linked neurodegenerative syndrome with congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration, linked to Xp22.33pter. Author(s): des Portes V, Bachner L, Bruls T, Beldjord C, Billuart P, Soufir N, Bienvenu T, Vinet MC, Malaspina E, Marchiani V, Bertini E, Kahn A, Franzoni E, Chelly J. Source: American Journal of Medical Genetics. 1996 July 12; 64(1): 69-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8826451&dopt=Abstract

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X-linked recessive atrophic macular degeneration from RPGR mutation. Author(s): Ayyagari R, Demirci FY, Liu J, Bingham EL, Stringham H, Kakuk LE, Boehnke M, Gorin MB, Richards JE, Sieving PA. Source: Genomics. 2002 August; 80(2): 166-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160730&dopt=Abstract

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Yellow dye laser thermotherapy of choroidal neovascularisation in age related macular degeneration. Author(s): Beintema MR, Oosterhuis JA, Hendrikse F. Source: The British Journal of Ophthalmology. 2001 June; 85(6): 708-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11371493&dopt=Abstract

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Young-Simpson syndrome comprising transient hypothyroidism, normal growth, macular degeneration and torticolis. Author(s): Kondoh T, Kinoshita E, Moriuchi H, Niikawa N, Matsumoto T, Masuno M. Source: American Journal of Medical Genetics. 2000 January 3; 90(1): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10602125&dopt=Abstract

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Zinc and copper metabolism in patients with senile macular degeneration. Author(s): Silverstone BZ, Landau L, Berson D, Sternbuch J. Source: Ann Ophthalmol. 1985 July; 17(7): 419-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4037602&dopt=Abstract

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Zinc and macular degeneration. Author(s): Beaumont P. Source: Archives of Ophthalmology. 1993 August; 111(8): 1023. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8352678&dopt=Abstract

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Zinc and macular degeneration. Author(s): Trempe CL. Source: Archives of Ophthalmology. 1992 November; 110(11): 1517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1444901&dopt=Abstract

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CHAPTER 2. NUTRITION AND MACULAR DEGENERATION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and macular degeneration.

Finding Nutrition Studies on Macular Degeneration The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “macular degeneration” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following is a typical result when searching for recently indexed consumer information on macular degeneration: •

Dietary carotenoids and certain cancers, heart disease, and age-related macular degeneration: a review of recent research. Author(s): Department of Regulatory and Clinical Development, Procter & Gamble Company, Cincinnati, OH 45224-1703, USA. Source: Cooper, D A Eldridge, A L Peters, J C Nutr-Revolume 1999 July; 57(7): 201-14 0029-6643

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Nutrition and macular degeneration. Source: Dysart, J.M. Nutr-M-D. Van Nuys, Calif. : PM, Inc. May 1992. volume 18 (5) page 1-2. 0732-0167

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Zinc and macular degeneration. Source: Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. July 1990. volume 48 (7) page 285-287. 0029-6643

The following information is typical of that found when using the “Full IBIDS Database” to search for “macular degeneration” (or a synonym): •

A novel relation of fatty acid with age-related macular degeneration. Author(s): Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kawaramachi, Hirokoji agaru, Kajiicho, Kamigyo-ku Kyoto City, Kyoto 602-8566, Japan. [email protected] Source: Ouchi, M Ikeda, T Nakamura, K Harino, S Kinoshita, S Ophthalmologica. 2002 Sep-October; 216(5): 363-7 0030-3755

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A2E and blue light in the retina: the paradigm of age-related macular degeneration. Author(s): Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), Zurich. Source: Shaban, H Richter, C Biol-Chem. 2002 Mar-April; 383(3-4): 537-45 1431-6730

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Age-related macular degeneration. Author(s): Vitreo-Retinal Foundation, Memphis, TN, USA. Source: Elfervig, L S Nurse-Pract-Forum. 1998 March; 9(1): 4-6 1045-5485

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Antioxidant vitamin and mineral supplementation for preventing age-related macular degeneration. Author(s): 'Glaxo' Department of Ophthalmology Epidemiology, Institute of Ophthalmology (UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD. [email protected] Source: Evans, J R Henshaw, K Cochrane-Database-Syst-Revolume 2000; (2): CD000253 1469-493X

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Are antioxidants or other supplements protective for age-related macular degeneration? Author(s): Retinal Vascular Center, Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Source: Fekrat, S Bressler, S B Curr-Opin-Ophthalmol. 1996 June; 7(3): 65-72 1040-8738

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Biochemical defects in retina-specific human ATP binding cassette transporter nucleotide binding domain 1 mutants associated with macular degeneration. Author(s): Department of Laboratory Sciences, Program in Biotechnology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Source: Suarez, Tatiana Biswas, Subhasis B Biswas, Esther E J-Biol-Chem. 2002 June 14; 277(24): 21759-67 0021-9258

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By the way doctor. I'm 72 and was recently told that I am losing a bit of my sight because of macular degeneration. My doctor assured me that it was progressing very slowly, but also said there wasn't really anything to do about it. But I read that zinc or vitamins might help. Should I be taking them? Source: Lee, Thomas H Harv-Health-Lett. 2002 February; 27(4): 8 1052-1577

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Can high-dose supplementation with vitamins C and E, beta carotene, and zinc slow the progression of macular degeneration? Author(s): Clarkson Family Practice Residency Program, Omaha, NE, USA. Source: Gordon, Josette E Schooff, Michael J-Fam-Pract. 2002 February; 51(2): 105 00943509

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Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration. Author(s): Wilmer Eye Institute, Baltimore, MD 21287-9115, USA. [email protected] Source: Lutty, G Grunwald, J Majji, A B Uyama, M Yoneya, S Mol-Vis. 1999 November 3; 535 1090-0535

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Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration. Author(s): Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston MA 02114, USA. [email protected] Source: Hammond, B R Wooten, B R Snodderly, D M Vision-Res. 1996 September; 36(18): 3003-9 0042-6989

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Could statins prevent age-related macular degeneration? Author(s): MRC Environmental Epidemiology Unit, University of Southampton & Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. [email protected] Source: Hall, N F Martyn, C N Expert-Opin-Pharmacother. 2002 July; 3(7): 803-7 14656566

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Current use of dietary supplementation in patients with age-related macular degeneration. Author(s): Department of Ophthalmology, University of Alberta, Edmonton, Alta. Source: Chang, C W Chu, G Hinz, B J Greve, M D Can-J-Ophthalmol. 2003 February; 38(1): 27-32 0008-4182

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Dietary prevention of age-related macular degeneration. Source: Pratt, S J-Am-Optom-Assoc. 1999 January; 70(1): 39-47 0003-0244

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Does coenzyme Q10 play a role in opposing oxidative stress in patients with agerelated macular degeneration? Author(s): Department of Ophthalmology, University of L'Aquila, L'Aquila, Italy. Source: Blasi, M A Bovina, C Carella, G Genova, M L Jansen, A M Lenaz, G Brancato, R Ophthalmologica. 2001 Jan-February; 215(1): 51-4 0030-3755

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Free radicals and antioxidant supplementation: a review of their roles in age-related macular degeneration. Author(s): Pacific University, College of Optometry, Forest Grove, OR 97116. Source: van der Hagen, A M Yolton, D P Kaminski, M S Yolton, R L J-Am-Optom-Assoc. 1993 December; 64(12): 871-8 0003-0244

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Ginkgo biloba extract for age-related macular degeneration. Author(s): 'Glaxo' Department of Ophthalmology Epidemiology, Institute of Ophthalmology (UCL) and Moorfields Eye Hospital, City Road, London, UK, EC1V 2PD. [email protected]

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Source: Evans, J R Cochrane-Database-Syst-Revolume 2000; (2): CD001775 1469-493X •

Implant radiotherapy for exudative macular degeneration associated with subretinal neovascularization. Author(s): New York Eye Cancer Center, New York, N.Y., USA. [email protected] Source: Finger, P T Front-Radiat-Ther-Oncol. 2001; 35: 86-93 0071-9679

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Interaction of A2E with model membranes. Implications to the pathogenesis of agerelated macular degeneration. Author(s): Howard Hughes Medical Institute, Laboratory of Molecular Biology and Biochemistry, The Rockefeller University, New York, NY 10021, USA. Source: De, S SakMarch, T P J-Gen-Physiol. 2002 August; 120(2): 147-57 0022-1295

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Is there a prevention and treatment strategy for macular degeneration? Author(s): VA Medical Center, N. Chicago, IL 60064. Source: Richer, S P J-Am-Optom-Assoc. 1993 December; 64(12): 838-50 0003-0244

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Lutein, zeaxanthin, and age-related macular degeneration. Source: Bruno, R.S. Medeiros, D.M. J-nutraceuticals-funct-med-foods. Binghamton, NY : Pharmaceutical Products Press, an imprint of the Haworth Press, Inc., c1997-. 2000. volume 3 (1) page 79-85. 1089-4179

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Macular degeneration in older adults. Author(s): Department of Nursing at Xavier University in Cincinnati, Ohio, USA. Source: Moore, L W Geriatr-Nurs. 2001 Mar-April; 22(2): 96-9 0197-4572

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Multicenter ophthalmic and nutritional age-related macular degeneration study--part 1: design, subjects and procedures. Author(s): Eye Clinic 112e, DVA Medical Center, North Chicago, IL 60064, USA. Source: Richer, S J-Am-Optom-Assoc. 1996 January; 67(1): 12-29 0003-0244

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Neovascular age-related macular degeneration and its relationship to antioxidant intake. Author(s): Department of Epidemiology and Biostatistics, University Medical Centre, Nijmegen, Netherlands. Source: Snellen, E L Verbeek, A L Van Den Hoogen, G W Cruysberg, J R Hoyng, C B Acta-Ophthalmol-Scand. 2002 August; 80(4): 368-71 1395-3907

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No efficacious treatment for age-related macular degeneration. Author(s): Department of Ophthalmology, Algemeen Ziekenhuis Sint-Jozef, Turnhout, Belgium. Source: Roodhooft, J Bull-Soc-Belge-Ophtalmol. 2000; 27683-92 0081-0746

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Nutritional supplement use and age-related macular degeneration. Author(s): National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA. Source: Chew, E Y Curr-Opin-Ophthalmol. 1995 June; 6(3): 19-24 1040-8738

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Oxidative damage and age-related macular degeneration. Author(s): Eye Research Institute, Oakland University, Rochester, MI 48309, USA. [email protected] Source: Winkler, B S Boulton, M E Gottsch, J D Sternberg, P Mol-Vis. 1999 November 3; 532 1090-0535

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Relationship between anticoagulant medication and massive intraocular hemorrhage in age-related macular degeneration. Author(s): Institute of Ophthalmology, University Hospital Nijmegen, The Netherlands. [email protected] Source: Tilanus, M A Vaandrager, W Cuypers, M H Verbeek, A M Hoyng, C B GraefesArch-Clin-Exp-Ophthalmol. 2000 June; 238(6): 482-5 0721-832X

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Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Author(s): Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. [email protected] Source: Bernstein, P S Zhao, D Y Wintch, S W Ermakov, I V McClane, R W Gellermann, W Ophthalmology. 2002 October; 109(10): 1780-7 0161-6420

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Risk factors for age-related macular degeneration. Author(s): Department of Epidemiology and International Eye Health, Institute of Ophthalmology, Bath street, EC1V 9EL, London, UK. [email protected] Source: Evans, J R Prog-Retin-Eye-Res. 2001 March; 20(2): 227-53 1350-9462

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Study of antiangiogenic agents with possible therapeutic applications in neoplastic disorders and macular degeneration. Author(s): Department of Internal Medicine, State University of NY at Buffalo Medical School-Kaleida Health Systems, 14203, USA. Source: Ambrus, J L Toumbis, C A Karakousis, C P Kulaylat, M Akhter, S Plavsic, L JMed. 2000; 31(5-6): 278-82 0025-7850

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Supplements may slow age-related macular degeneration. Source: Anonymous Mayo-Clin-Health-Lett. 2002 March; 20(3): 4 0741-6245

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Tetrathiomolybdate as an antiangiogenesis therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration. Author(s): Department of Ophthalmology and Visual Sciences, University of Michigan Medical Center, Ann Arbor, USA. Source: Vine, A K Brewer, G J Trans-Am-Ophthalmol-Soc. 2002; 100: 73-6; discussion 767 0065-9533

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The macular pigment: a possible role in protection from age-related macular degeneration. Author(s): Department of Chemistry, Florida International University, Miami 33199, USA. Source: Landrum, J T Bone, R A Kilburn, M D Adv-Pharmacol. 1997; 38537-56 1054-3589

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Treatment of macular degeneration, according to Bangerter. Author(s): King Khaled Eye Specialist Hospital P.O. Box Riyadh 7191, Riyadh 11 462 Kingdom of Saudi Arabia ++966 1/482 1234 ++966 1/482 1908. Source: Teichmann, K D Eur-J-Med-Res. 1997 October 30; 2(10): 445-54 0949-2321

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Verteporfin therapy of subfoveal choroidal neovascularization in patients with agerelated macular degeneration: additional information regarding baseline lesion composition's impact on vision outcomes-TAP report No. 3. Author(s): Wilmer Photograph Reading Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2002, USA. [email protected] Source: Bressler, N M Arnold, J Benchaboune, M Blumenkranz, M S Fish, G E Gragoudas, E S Lewis, H Schmidt Erfurth, U Slakter, J S Bressler, S B Manos, K Hao, Y

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Hayes, L Koester, J Reaves, A Strong, H A Arch-Ophthalmol. 2002 November; 120(11): 1443-54 0003-9950 •

Visaline in the treatment of age-related macular degeneration: a pilot study. Author(s): University Eye Clinic, Basle, Switzerland. Source: Kaiser, H J Flammer, J Stumpfig, D Hendrickson, P Ophthalmologica. 1995; 209(6): 302-5 0030-3755

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Vitamins for cataracts and macular degeneration. Source: Eichenbaum, J W J-Ophthalmic-Nurs-Technol. 1996 Mar-April; 15(2): 65-7 07447132

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

Nutrition

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Open Directory Project: http://dmoz.org/Health/Nutrition/

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to macular degeneration; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Vitamins Multiple Vitamin-mineral Supplements Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin C Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,904,00.html Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Alternative names: Alpha-Tocopherol, Beta-Tocopherol, D-Alpha-Tocopherol, Delta-Tocopherol, Gamma-Tocopherol Source: Integrative Medicine Communications; www.drkoop.com Vitamin E Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin E Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,906,00.html

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Minerals Alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Beta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com

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D-alpha-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Delta-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Gamma-tocopherol Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com Zinc Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10071,00.html Zinc/copper Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,938,00.html •

Food and Diet Arugula Source: Healthnotes, Inc.; www.healthnotes.com Asparagus Source: Healthnotes, Inc.; www.healthnotes.com Beets Source: Healthnotes, Inc.; www.healthnotes.com Bok Choy Source: Healthnotes, Inc.; www.healthnotes.com

Nutrition

Broccoli Source: Healthnotes, Inc.; www.healthnotes.com Carrots Source: Healthnotes, Inc.; www.healthnotes.com Chicory Source: Healthnotes, Inc.; www.healthnotes.com Collards Source: Healthnotes, Inc.; www.healthnotes.com Dandelion Greens Source: Healthnotes, Inc.; www.healthnotes.com Endive Source: Healthnotes, Inc.; www.healthnotes.com Kale Source: Healthnotes, Inc.; www.healthnotes.com Kohlrabi Source: Healthnotes, Inc.; www.healthnotes.com Mustard Greens Source: Healthnotes, Inc.; www.healthnotes.com Spinach Source: Healthnotes, Inc.; www.healthnotes.com Summer Squash Source: Healthnotes, Inc.; www.healthnotes.com Sweet Peppers Source: Healthnotes, Inc.; www.healthnotes.com Sweet Potatoes Source: Healthnotes, Inc.; www.healthnotes.com Tomatoes Source: Healthnotes, Inc.; www.healthnotes.com Turnips Source: Healthnotes, Inc.; www.healthnotes.com Winter Squash Source: Healthnotes, Inc.; www.healthnotes.com Yams Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND MACULAR DEGENERATION Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to macular degeneration. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “macular degeneration” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •

Antioxidant Vitamins and Zinc Reduce Risk of Vision Loss from Age-Related Macular Degeneration Source: Bethesda, MD: National Eye Institute. 2001. 5 p. Contact: Available from National Eye Institute. National Institutes of Health, 2020 Vision Place, Bethesda, MD 20892. (301) 496-5248. PRICE: Free. Summary: This National Eye Institute (NEI) news release reports on the nationwide clinical trial "Age Related Eye Disease Study," which found that high levels of antioxidants and zinc reduce the risk of advanced age-related macular degeneration and its associated vision loss. It describes the methodology and results of the trial, and includes quotes from the trial investigators and the director of the NEI.

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National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to macular degeneration and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “macular degeneration” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to macular degeneration: •

A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Author(s): Age-Related Eye Disease Study Research Group. Source: Archives of Ophthalmology. 2001 October; 119(10): 1417-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594942&dopt=Abstract

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Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials. Author(s): Bartlett H, Eperjesi F. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2003 September; 23(5): 383-99. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12950886&dopt=Abstract

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Age-related macular degeneration: a randomized clinical trial of a self-management intervention. Author(s): Brody BL, Williams RA, Thomas RG, Kaplan RM, Chu RM, Brown SI. Source: Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine. 1999 Fall; 21(4): 322-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10721440&dopt=Abstract

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Alternative therapies in exudative age related macular degeneration. Author(s): Chong NH, Bird AC. Source: The British Journal of Ophthalmology. 1998 December; 82(12): 1441-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9930280&dopt=Abstract

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Antioxidant vitamin and mineral supplementation for preventing age-related macular degeneration. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11869572

Author(s): Cochrane Database Syst Rev. 2002;(1):CD000254 Source: Cochrane Database Syst Rev. 2000; (2): Cd000253. Review. <Title>Antioxidant vitamin and mineral supplements for age-related macular degeneration. Author(s): Evans JR.

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Source: Cochrane Database Syst Rev. 2002; (2): Cd000254. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12076389&dopt=Abstract •

Antioxidant vitamin and mineral supplements for age-related macular degeneration. Author(s): Evans JR. Source: Cochrane Database Syst Rev. 2002; (1): Cd000254. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869572&dopt=Abstract

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Antioxidant vitamin and mineral supplements for age-related macular degeneration. Author(s): Evans JR. Source: Cochrane Database Syst Rev. 2000; (2): Cd000254. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796708&dopt=Abstract

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Antioxidants and zinc to prevent progression of age-related macular degeneration. Author(s): Jampol LM, Ferris FL 3rd. Source: Jama : the Journal of the American Medical Association. 2001 November 21; 286(19): 2466-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11759670&dopt=Abstract

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Antioxidants, zinc, and age-related macular degeneration: results and recommendations. Author(s): Jampol LM. Source: Archives of Ophthalmology. 2001 October; 119(10): 1533-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11594957&dopt=Abstract

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Benefit of coloured lenses for age-related macular degeneration. Author(s): Wolffsohn JS, Dinardo C, Vingrys AJ. Source: Ophthalmic & Physiological Optics : the Journal of the British College of Ophthalmic Opticians (Optometrists). 2002 July; 22(4): 300-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162481&dopt=Abstract

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Can high-dose supplementation with vitamins C and E, beta carotene, and zinc slow the progression of macular degeneration? Author(s): Gordon JE, Schooff M. Source: The Journal of Family Practice. 2002 February; 51(2): 105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978202&dopt=Abstract

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Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration. Author(s): Lutty G, Grunwald J, Majji AB, Uyama M, Yoneya S.

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Source: Molecular Vision [electronic Resource]. 1999 November 3; 5: 35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10562659&dopt=Abstract •

Changing therapeutic paradigms for exudative age-related macular degeneration: antiangiogenic agents and photodynamic therapy. Author(s): Ciulla TA, Danis RP, Criswell M, Pratt LM. Source: Expert Opinion on Investigational Drugs. 1999 December; 8(12): 2173-2182. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11139846&dopt=Abstract

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Clinical management of age-related macular degeneration: room for improvement. Author(s): Howe LJ. Source: Eye (London, England). 1995; 9 ( Pt 6 Su): 42-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8729019&dopt=Abstract

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Complex visual hallucinations in macular degeneration. Author(s): Lalla D, Primeau F. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1993 November; 38(9): 584-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8306229&dopt=Abstract

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Current use of dietary supplementation in patients with age-related macular degeneration. Author(s): Chang CW, Chu G, Hinz BJ, Greve MD. Source: Can J Ophthalmol. 2003 February; 38(1): 27-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12608514&dopt=Abstract

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Dietary fat and risk for advanced age-related macular degeneration. Author(s): Seddon JM, Rosner B, Sperduto RD, Yannuzzi L, Haller JA, Blair NP, Willett W. Source: Archives of Ophthalmology. 2001 August; 119(8): 1191-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483088&dopt=Abstract

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Free radicals and antioxidant supplementation: a review of their roles in age-related macular degeneration. Author(s): van der Hagen AM, Yolton DP, Kaminski MS, Yolton RL. Source: J Am Optom Assoc. 1993 December; 64(12): 871-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8308191&dopt=Abstract

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Ginkgo biloba extract for age-related macular degeneration. Author(s): Evans JR.

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Source: Cochrane Database Syst Rev. 2000; (2): Cd001775. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796819&dopt=Abstract •

High-dose supplements for age-related macular degeneration: did you leave out centrum? Author(s): Abramson DH, Abramson HS. Source: Archives of Ophthalmology. 2002 November; 120(11): 1602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427092&dopt=Abstract

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Information about age-related macular degeneration on the Internet. Author(s): Stone TW, Jumper JM. Source: Southern Medical Journal. 2001 January; 94(1): 22-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11213937&dopt=Abstract

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Macular degeneration in older adults. Author(s): Moore LW. Source: Geriatric Nursing (New York, N.Y.). 2001 March-April; 22(2): 96-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11326218&dopt=Abstract

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Macular degeneration. A devastating but treatable disease. Author(s): Farber ME, Farber AS. Source: Postgraduate Medicine. 1990 August; 88(2): 181-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2381881&dopt=Abstract

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Management of age related macular degeneration: still room for improvement. Author(s): Howe LJ. Source: The British Journal of Ophthalmology. 2003 March; 87(3): 375. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12598473&dopt=Abstract

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Nutritional supplement use and age-related macular degeneration. Author(s): Chew EY. Source: Current Opinion in Ophthalmology. 1995 June; 6(3): 19-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10150867&dopt=Abstract

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Prospective study of dietary fat and the risk of age-related macular degeneration. Author(s): Cho E, Hung S, Willett WC, Spiegelman D, Rimm EB, Seddon JM, Colditz GA, Hankinson SE. Source: The American Journal of Clinical Nutrition. 2001 February; 73(2): 209-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11157315&dopt=Abstract

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Prospective study of zinc intake and the risk of age-related macular degeneration. Author(s): Cho E, Stampfer MJ, Seddon JM, Hung S, Spiegelman D, Rimm EB, Willett WC, Hankinson SE. Source: Annals of Epidemiology. 2001 July; 11(5): 328-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399447&dopt=Abstract

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Resonance Raman measurement of macular carotenoids in normal subjects and in age-related macular degeneration patients. Author(s): Bernstein PS, Zhao DY, Wintch SW, Ermakov IV, McClane RW, Gellermann W. Source: Ophthalmology. 2002 October; 109(10): 1780-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359594&dopt=Abstract

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Retinal pigment epithelial debridement as a model for the pathogenesis and treatment of macular degeneration. Author(s): Del Priore LV, Kaplan HJ, Hornbeck R, Jones Z, Swinn M. Source: American Journal of Ophthalmology. 1996 November; 122(5): 629-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8909202&dopt=Abstract

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Risk factors for age-related macular degeneration: an update. Author(s): Hyman L, Neborsky R. Source: Current Opinion in Ophthalmology. 2002 June; 13(3): 171-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12011686&dopt=Abstract

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Senile macular degeneration and psychosis. Author(s): Casey DA, Wandzilak T. Source: Journal of Geriatric Psychiatry and Neurology. 1988 April-June; 1(2): 108-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3252878&dopt=Abstract

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Serum iron, transferrin saturation, ferritin, and dietary data in age-related macular degeneration. Author(s): Richer S, Rudy D, Statkute L, Karofty K, Frankowski J. Source: American Journal of Therapeutics. 2002 January-February; 9(1): 25-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782816&dopt=Abstract

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The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: the Age-Related Eye Disease Study Report Number 6. Author(s): Age-Related Eye Disease Study Research Group. Source: American Journal of Ophthalmology. 2001 November; 132(5): 668-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704028&dopt=Abstract

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The potential preventive effects of vitamins for cataract and age-related macular degeneration. Author(s): Jacques PF. Source: Int J Vitam Nutr Res. 1999 May; 69(3): 198-205. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389028&dopt=Abstract

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Visual hallucinations in patients with macular degeneration. Author(s): Holroyd S, Rabins PV, Finkelstein D, Nicholson MC, Chase GA, Wisniewski SC. Source: The American Journal of Psychiatry. 1992 December; 149(12): 1701-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1443247&dopt=Abstract

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Vitamin E supplementation and macular degeneration: randomised controlled trial. Author(s): Taylor HR, Tikellis G, Robman LD, McCarty CA, McNeil JJ. Source: Bmj (Clinical Research Ed.). 2002 July 6; 325(7354): 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098721&dopt=Abstract

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Who should receive oral supplement treatment for age-related macular degeneration? Author(s): McBee WL, Lindblad AS, Ferris FL 3rd. Source: Current Opinion in Ophthalmology. 2003 June; 14(3): 159-62. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12777936&dopt=Abstract

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Zinc supplementation for macular degeneration. Author(s): Hawkins WR. Source: Archives of Ophthalmology. 1991 October; 109(10): 1345. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1929912&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

•

Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

•

HealthGate: http://www.tnp.com/

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to macular degeneration; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Macular Degeneration Source: Healthnotes, Inc.; www.healthnotes.com Macular Degeneration Source: Integrative Medicine Communications; www.drkoop.com Macular Degeneration Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Retinopathy Source: Healthnotes, Inc.; www.healthnotes.com

•

Herbs and Supplements Alpha-lipoic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10002,00.html Beta-carotene Source: Healthnotes, Inc.; www.healthnotes.com Beta-carotene Source: Prima Communications, Inc.www.personalhealthzone.com Bilberry Alternative names: Vaccinium myrtillus Source: Healthnotes, Inc.; www.healthnotes.com Bilberry Source: Prima Communications, Inc.www.personalhealthzone.com

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Bilberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10007,00.html Carotenoids Source: Healthnotes, Inc.; www.healthnotes.com Carotenoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,763,00.html Coenzyme Q Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,768,00.html EDTA Source: Integrative Medicine Communications; www.drkoop.com Ethylenediaminetetraacetic Acid (EDTA) Source: Integrative Medicine Communications; www.drkoop.com Flavonoids Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Grape Seed Alternative names: Vitis vinifera Source: Integrative Medicine Communications; www.drkoop.com Grape Seed Extract Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,793,00.html

126 Macular Degeneration

Lutein Source: Healthnotes, Inc.; www.healthnotes.com Lutein Source: Prima Communications, Inc.www.personalhealthzone.com Lycopene Source: Healthnotes, Inc.; www.healthnotes.com Lycopene Source: Prima Communications, Inc.www.personalhealthzone.com NAC (N-acetylcysteine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,809,00.html OPCS (oligomeric Proanthocyanidins) Source: Prima Communications, Inc.www.personalhealthzone.com Vitis Vinifera Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DEGENERATION

DISSERTATIONS

ON

MACULAR

Overview In this chapter, we will give you a bibliography on recent dissertations relating to macular degeneration. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “macular degeneration” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on macular degeneration, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Macular Degeneration ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to macular degeneration. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Age-related Macular Degeneration: Neuropsychological Differences in Scores between Successful and Unsuccessful CCTV Users on Selected Tests by Kruger, Daniel E.; PhD from The University of Arizona, 2002, 101 pages http://wwwlib.umi.com/dissertations/fullcit/3060984

•

Analysis of the Gene and Protein Causing Best Macular Dystrophy by Bakall, Benjamin; PhD from Uppsala Universitet (Sweden), 2003, 42 pages http://wwwlib.umi.com/dissertations/fullcit/f30577

•

Associations among Comorbidities, Visual Acuity, and Quality of Life in Patients with Age-related Macular Degeneration and Central Vision Loss by Miskala, Paivi Helena; PhD from The Johns Hopkins University, 2002, 143 pages http://wwwlib.umi.com/dissertations/fullcit/3046519

128 Macular Degeneration

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

129

CHAPTER 5. CLINICAL DEGENERATION

TRIALS

AND

MACULAR

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning macular degeneration.

Recent Trials on Macular Degeneration The following is a list of recent trials dedicated to macular degeneration.8 Further information on a trial is available at the Web site indicated. •

An evaluation of safety and efficacy of Anecortave Acetate versus placebo in patients with subfoveal CNV due to exudative AMD. Condition(s): Macular Degeneration; Maculopathy, Age-Related Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To demonstrate that anecortave acetate is superior to placebo in maintenance of visual acuity at the 12- and 24-month visits. Phase(s): Phase III Study Type: Interventional Contact(s): Alcon Clinical 817-568-6747 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00058994

•

An evaluation of safety and efficacy of Anecortave Acetate vs. placebo in patients with subfoveal choroidal neovascularization(CNV) due to wet age-related macular degeneration(AMD) Condition(s): Macular Degeneration; Maculopathy, Age-Related; Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related

8

These are listed at www.ClinicalTrials.gov.

Age-Related

130 Macular Degeneration

Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: To demonstrate that anecortave acetate is superior to placebo in maintenance of visual acuity at the 12- and 24-month visits. Phase(s): Phase III Study Type: Interventional Contact(s): Alcon Clinical 817-568-6747 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00051129 •

Celecoxib to Treat Macular Degeneration in Patients Receiving Photodynamic Therapy Condition(s): Macular Degeneration Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will determine whether the drug celecoxib (Celebrex(r) (Registered Trademark)) can help stabilize or improve vision in patients with agerelated macular degeneration (AMD) who are receiving photodynamic therapy, or PDT (also called cold laser treatment). The macula is the part of the retina in the back of the eye that determines central or best vision. AMD can severely impair central vision, affecting a person's ability to read, drive, and carry out daily activities. This vision loss is caused by the formation of abnormal new blood vessels in the choroid-a thin, pigmented vascular layer of the eye behind the retina-that leak blood under the macula. PTD stops the growth of these blood vessels and slows the rate of vision loss. However, the treatment usually does not cause vision to improve, and it has only a temporary effect, requiring several treatments over 2 years. Furthermore, PDT does not work in all patients and may actually cause some swelling and re-growth of blood vessels. Celecoxib is an anti-inflammatory drug that, in animal studies, has prevented the growth of abnormal blood vessels associated with tumors and with injury to the cornea. Thus, the drug might reduce swelling and prevent vessel re-growth in AMD, enhancing the effectiveness of PDT. Patients 55 years of age and older with AMD and visual acuity of 20/20 to 20/200 may be eligible for this study. Participants will be randomly assigned to take either celecoxib or a placebo (a look-alike pill with no active drug) twice a day and undergo the various tests and procedures detailed below. Not every examination will be done at every visit, but all may be required at one visit. -Medical history and physical examination -Blood drawing: A blood sample is drawn from an arm vein to evaluate liver and kidney function -Eye examination: Visual acuity and eye pressure are measured, and the lens, retina, pupils and eye movements are examined -Photography: Photographs of the eye are taken using a special camera with a bright flash -Fluorescein angiography: Pictures of the retina are taken to look for abnormal blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. The retina is photographed using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality. -Indocyanine green angiography: This procedure, similar to fluorescein angiography, uses a green dye to photograph the retina and identify portions of abnormal vessels in the deepest part of the retina. -Optical coherence tomography: This new technique uses light to produce a 2-dimensional cross-sectional picture of the retina. The patient looks into a machine called an optical coherence tomograph at a pattern of flashing and rotating red and green lights, first with one eye

Clinical Trials 131

and then the other. One week after starting the study medications, laser treatment will begin. For this procedure, a needle is placed in an arm vein and a chemical called verteporfin (Visudyne(r) (Registered Trademark)) is infused into the vein over 10 minutes. After 15 minutes, the eye is anesthetized with numbing drops. A special contact lens is then placed on the eye and the laser beam is directed to the eye for 83 seconds. Patients will be followed in the clinic every 6 weeks for 36 weeks for various examinations and possible re-treatment, if needed. Some patients will be asked to return 1 to 2 weeks after the first PDT for an eye examination and fluorescein angiography. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00043680 •

Effect of DHA Supplements on Macular Function in Patients with Stargardt Macular Dystrophy and Stargardt-like Macular Dystrophy Condition(s): Macular Degeneration Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will evaluate whether docosahexaenoic acid (DHA) dietary supplementation can improve macular function in patients with Stargardt macular dystrophy and Stargardt-like macular dystrophy. Stargardt macular dystrophy is a recessive inherited trait that causes a severe form of macular degeneration. (The macula is the center part of the retina in the back of the eye that is responsible for fine vision.) The disorder begins in late childhood and progresses to a significant decrease in central vision. One of the earliest signs of the disorder is accumulation in and under the macula of a fatty pigment called lipofuscin. Stargardt-like macular dystrophy is a dominant inherited trait involving loss of central vision, but it begins later than Stargardt macular dystrophy, and the accumulation of lipofuscin extends beyond the central region of the macula. DHA is a fatty acid that is essential for normal brain and eye development. It is normally found in the diet, but not in large amounts. Supplements may help prevent or slow the progression of some eye diseases. Patients with autosomal dominant Stargardt-like macular dystrophy or autosomal recessive Stargardt macular dystrophy are eligible for this study. Candidates will be screened with the following tests and procedures: - Medical history and physical examination. Blood test to measure levels of DHA and vitamins. - Eye examination: The patient's vision and eye pressure are tested, then the pupils are dilated to examine structures inside the eye. Photographs are also taken. - Visual field test: The patient looks at a tiny spot of light projected onto a white screen and is asked to note when other lights appear at other places on the screen. - Electroretinogram (ERG): An electrode (small silver disk) is taped to the patient's forehead. Drops are given to numb the eyes and special contact lenses are inserted in the eyes. For the first part of the test, the patient looks at the center of a black and white checkerboard screen that flickers for 30 seconds at a time. This is repeated 16 or more times. For the second part of the test, the patient looks inside a sphere, in which flashes of light flicker for 20 seconds at a time. This is repeated four or more times. The contact lenses sense small electrical signals generated by the retina during the tests. Participants will begin taking DHA capsules or a placebo (look-alike capsules with no active ingredient) from 1 week to 3 months after enrolling in the study and will repeat several of the screening tests at follow-up visits scheduled 3, 6, 9, 12, and

132 Macular Degeneration

15 months after they start taking the capsules. They will also be interviewed about any treatment side effects. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060749 •

Efficacy and Safety Study of rhuFab V2 (Ranibizumab) to Treat Age-Related Macular Degeneration Condition(s): Age-Related Maculopathy Study Status: This study is currently recruiting patients. Sponsor(s): Genentech Purpose - Excerpt: The purpose of this study is to determine whether injections of rhuFab into the eye can prevent vision loss in patients with age-related macular degeneration, and also to evaluate the safety of this treatment. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056836

•

Genetic Factors in Age-Related Macular Degeneration Condition(s): Macular Degeneration Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will examine whether certain polymorphisms (small gene variances) predispose people to develop age-related macular degeneration (AMD). This eye condition affects people over 50 years of age and can cause permanent loss of central vision. The study will examine and compare the frequency of polymorphisms in patients with AMD to that of individuals without AMD. This information will help identify genetic risk factors for the AMD and may lead to the development of more effective treatments. Patients 50 years of age and older with advanced AMD and healthy normal volunteers may be eligible for this study. All participants will provide an eye health history and will have 10 milliliters (2 teaspoons) of blood drawn from an arm vein. The DNA in the blood will be isolated and tested for certain genes that other research indicates are important in aging and age-related diseases. The normal and polymorphic gene sequences will be identified and compared in patients with AMD and control subjects to determine if any of the polymorphisms are related to development of AMD. In addition, control subjects will have a routine eye examination, including dilation of the pupils for examination of the back of the eye. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00058695

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•

Identification and Treatment of Feeder Vessels in Macular Degeneration Condition(s): Macular Degeneration Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will try to identify and treat feeder vessels in age-related macular degeneration. The macula is the part of the retina in the back of the eye that determines central or best vision. In macular degeneration, leaking blood vessels under the macula lead to loss of central vision. These vessels branch out tree-like from one or more feeder vessels. Instead of treating all the abnormal branching vessels, this study will try to find and close only the feeder vessels, thereby depriving the abnormal vessels of nutrition. The vessels will be closed with laser beam treatment. People 50 years of age and older with macular degeneration and visual acuity worse than 20/50 in the study eye and the same or better vision in the other eye may be eligible for this study. Candidates will undergo fluorescein angiography to try to locate feeder vessels. For this procedure, a yellow dye is injected into an arm vein. The dye travels to the blood vessels in the eyes, and pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality. Before laser treatment, participants will have a complete eye examination, including measurement of visual acuity, evaluation of the front part of the eye with a slit lamp microscope, examination of the retina with an ophthalmoscope, and measurement of eye pressure using a tonometer. During the laser treatment phase of the study, participants will have indocyanine green angiography-a procedure similar to fluorescein angiography, but using a green dye-to photograph the retina and identify feeder vessels. If feeder vessels are located, laser beam treatment will begin. For this procedure, the eye is anesthetized with numbing drops. A special contact lens is then placed on the eye for the laser treatment. The number of treatments depends on how well the individual patient responds, but usually between two and eight treatments are required. The indocyanine green angiogram will be repeated after the laser beam treatment to determine if the feeder vessels have been successfully closed. If the vessels remain partially open, a repeat application will be done, followed by another indocyanine green angiogram to check the results. Patients will be checked in the clinic after 1 week to see if additional treatment is needed. If so, re-treatment will be done in a week. If no re-treatment is required, follow-up visits will be scheduled 2, 3, and 6 weeks after treatment, 3 and 6 months after treatment, and every 6 months after that for 2 years to evaluate treatment results. The evaluations will include fluorescein angiograms and other examinations that were done before starting treatment. If abnormal vessels are still present or growing, repeat treatments will be applied following the same procedure. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018070

•

Laser and Medical Treatment of Diabetic Macular Edema Condition(s): Macular Degeneration Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI)

134 Macular Degeneration

Purpose - Excerpt: This study will compare the side effects of two laser treatments for diabetic macular edema, a common condition in patients with diabetes. In macular edema, blood vessels in the retina, a thin layer of tissue that lines the back of the eye become leaky and the retina swells. The macula, the center part of the retina that is responsible for fine vision may also swell, causing vision loss. Traditional laser treatment (argon blue or green or yellow) for macular swelling, or edema, causes scarring that can expand and possibly lead to more loss of vision. Studies with a different type of laser (diode) may be less damaging. The results of this study on side effects of the treatments will be used to design a larger study of effectiveness. This study will also examine whether celecoxib (Celebrex(r) (Registered Trademark)), an antiarthritis drug that reduces inflammation and swelling, can reduce inflammation and swelling of the retina. Patients with elevated cholesterol levels will be invited to participate in a cholesterol reduction part of the study to compare normal-pace cholesterol reduction with accelerated reduction. Patients 18 years of age and older with type 1 or type 2 diabetes and macular edema that requires laser treatment may be eligible for this study. Candidates will be screened with the following tests and procedures: - Medical history: to review past medical conditions and treatments. Physical examination: to measure vital signs (pulse, blood pressure, temperature, breathing rate) and examine the head and neck, heart, lungs, abdomen, arms and legs. Eye examination: to assess visual acuity (eye chart test) and examine pupils, lens, retina, and eye movements. The pupils will be dilated with drops for this examination. - Blood tests: to measure cholesterol, blood clotting time, hemoglobin A1C (a measure of diabetes control), and to evaluate liver and kidney function. - Eye photography: to help evaluate the status of the retina and changes that may occur in the future. Special photographs of the inside of the eye are taken using a camera that flashes a bright light into the eye. From 2 to 20 pictures may be taken, depending on the eye condition. Fluorescein angiography: to evaluate the eye's blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality. Participants will be randomly assigned to take celecoxib or placebo (an inactive, lookalike pill). Participants who have elevated cholesterol levels may return for a brief visit after 1 month. All patients will return for follow-up visits at 3, 6, and 12 months. Patients who require laser treatment will be randomly assigned to one of the two laser treatments. For these procedures, eye drops are put in the eye to numb the surface and a contact lens is placed on the eye during the laser beam application. Several visits may be required for additional laser treatments. The maximum number of treatments depends on how well the treatment is working. Patients who respond well to the study medication may receive no laser treatments. After the first year, patients will be followed every 6 months until either the patient returns for a 3-year visit, the last enrolled patient returns for the 1-year visit, or the patient requests to leave the study. During the follow-up visits, patients' response to treatment will be evaluated with repeat tests of several of the screening exams. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050479

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•

Open-Label Posterior Juxtacleral Injections of Anecortave Acetate 15mg Dose for Long Term Use in Patients with AMD Condition(s): Macular Degeneration Study Status: This study is currently recruiting patients. Sponsor(s): Alcon Research Purpose - Excerpt: A 24 month study of posterior juxtascleral injections of open label Anecortave Acetate 15mg administered every 6 months. Phase(s): Phase III Study Type: Interventional Contact(s): Alcon Call Center 866-692-5959 [email protected]; Alcon Clinical (817)568-6747 [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00065728

•

Pilot Study of Intravitreal Injection of Triamcinolone Acetonide Formulation for Retinal Vascular Disorders Condition(s): Macular Degeneration; Retinal Vein Occlusion Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: The use of intravitreal injections of corticosteroid (triamcinolone acetonide) appears to be a promising treatment for a variety of ocular diseases associated with inflammation. To date, the only drug available, 'Kenalog-40 Injection' produced by Bristol Myers Squibb, has not been formulated for intraocular use. This formulation when used intraocularly has been associated with cases of non-bacterial endophthalmitis, which is thought to be due to the presence of benzyl alcohol and/or polysorbate 80. Both are suspected irritants. The purpose of this study is to evaluate the safety of a novel preservative-free formulation of triamcinolone acetonide (TAC-PF) at four dosage levels. The study will be an open-label, single-masked, randomized Phase I study that will investigate the safety and potential efficacy of the new formulation of TAC-PF. Sixteen participants with retinal vascular disease will be randomly assigned to receive via intravitreal injection at one of 4 dose levels (1 mg, 4 mg, 8 mg, or 16 mg) of TAC-PF. Depending on a participant's response, injections may be repeated at up to 3 month intervals. Participants will be followed for 3 years. The primary outcome will be an assessment of post-injection intraocular toxicity related events including increased inflammation, increased intraocular pressure, significant decreases in BCVA, cataract formation, retinal detachment, and intraocular hemorrhage. The secondary outcomes will be an improvement of 15 letters in best-corrected visual acuity (BCVA, ETDRS) from baseline to year 3, and decreases in retinal thickening and area of leakage. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00071227

•

Preventing Depression in Patients with Macular Degeneration Condition(s): Depression; Macular Degeneration Study Status: This study is currently recruiting patients.

136 Macular Degeneration

Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the efficacy of a brief, standardized cognitive psychotherapy called Problem Solving Treatment (PST) to prevent depression in elderly patients with age-related macular degeneration (AMD). Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00042211 •

Safety & Efficacy Study of rhuFab V2 in Combination with Verteporfin for treatment of Age-related Macular Degeneration Condition(s): Age-Related Maculopathy Study Status: This study is currently recruiting patients. Sponsor(s): Genentech Purpose - Excerpt: The primary purpose of this study is to determine if injections of rhuFab V2 into the eye in combination with verteporfin photodynamic therapy is a safe and efficacious treatment for patients with age-related macular degeneration. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056823

•

Safety and Efficacy Study of rhuFAb V2 (Ranibizumab) to Treat Age-Related Macular Degeneration Condition(s): Age-Related Maculopathy Study Status: This study is currently recruiting patients. Sponsor(s): Genentech Purpose - Excerpt: The purpose of this study is to evaluate the safety and efficacy of Lucentis (ranibizumab) compared with verteporfin photodynamic therapy in preventing vision loss associated with age-related macular degeneration. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00061594

•

Screening for Studies on Retinovascular Diseases Condition(s): Diabetic Retinopathy; Neovascularization; Retinal Disease

Macular

Degeneration;

Pathologic

Study Status: This study is currently recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This screening protocol is designed to help recruit patients for National Eye Institute (NEI) studies of the retina, such as diabetic retinopathy and macular degeneration. Patients must meet the specific criteria of a research study, and

Clinical Trials 137

this protocol serves as a first step for admitting patients to a retinal disease study. Candidates will undergo a medical history and comprehensive eye examination. The eye examination includes dilation of the pupils to fully examine the retina. In some studies, photographs of the eye are required. This is done using fluorescein angiography. In this procedure, a dye called sodium fluorescein is injected into the blood stream through a vein. After the dye reaches the blood vessels of the eye, photographs are taken of the retina. Other diagnostic procedures may include physical examination, questionnaires, routine laboratory tests and other standard or specialized tests, as needed. When the screening is completed, patients will be informed of their options to participate in a study. Patients who are ineligible for a current study will be informed of alternative treatments or options. No treatment is offered under this protocol. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001733 •

A Study to Evaluate Retisert in the Treatment of Patients with the "wet" form of AgeRelated Macular Degeneration Condition(s): Macular Degeneration Study Status: This study is no longer recruiting patients. Sponsor(s): Control Delivery Systems; Bausch & Lomb Pharmaceuticals Purpose - Excerpt: A study evaluating Retisert in patients with age-related macular degeneration Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00032396

•

Age-Related Eye Disease Study (AREDS) Condition(s): Macular Degeneration; Cataract; Lens Opacities Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To assess the clinical course, prognosis, and risk factors of age-related macular degeneration (AMD) and cataract. To evaluate, in randomized clinical trials, the effects of pharmacologic doses of (1) antioxidants and zinc on the progression of AMD and (2) antioxidants on the development and progression of lens opacities. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000145

•

Age-Related Macular Degeneration and Cataract Condition(s): Cataract; Macular Degeneration

138 Macular Degeneration

Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: Clouding of the lens, or cataract formation, accounts for vision loss in about 45 percent of the U.S. population aged 75 to 85 years. Macular degenerationdestruction of the part of the retina responsible for central vision used in reading-is the leading cause of legal blindness in people over 60 years of age. This 10-year study on age-related macular degeneration and cataract will investigate: 1. The natural course and prognosis of these diseases; 2. The effects of vitamin and mineral supplements on their development and progression; and 3. Risk factors associated with their development. Patients with age-related macular degeneration or cataract will be evaluated for their eligibility in this study with a medical history, vision test and thorough eye examination, including photographs of the lens and back of the eye. Those accepted to the study will be randomly assigned to take one of the following 4 times a day: 1) a vitamin only; 2) a mineral only; 3) both a vitamin and a mineral; or 4) a placebo (a tablet with no active ingredient). A blood sample will be drawn at the beginning of the study and once a year until its end to measure vitamin and mineral blood levels and to study their effects on cholesterol. Participants will be asked to complete a voluntary questionnaire about their visual function and how it affects their daily lives. Some patients may be asked to participate in two interviews about 6 months apart, in which they will provide information on their food intake over a 24-hour period. This information will be used to explore possible dietary risk factors for macular degeneration and cataract. Participants may also be asked to provide a small blood sample for use in studying possible hereditary factors associated with age-related macular degeneration. This research may lead to a better understanding of why the condition develops, who is likely to be affected and to what degree, and how to improve treatment. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001312 •

Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Condition(s): Macular Degeneration Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether application of low-intensity laser treatment of eyes with drusen in the macula can prevent later complications of age-related macular degeneration and thereby preserve visual function. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000167

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Macular Photocoagulation Study (MPS) Condition(s): Choroidal Neovascularization; Macular Degeneration; Histoplasmosis

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Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To evaluate laser treatment of choroidal neovascularization (CNV) through randomized, controlled clinical trials. The Macular Photocoagulation Study (MPS) consisted of three sets of randomized, controlled clinical trials. Change in bestcorrected visual acuity from baseline was the primary outcome for all MPS trials. Other measures of vision are evaluated in each set of trials. The purpose of each is described below. Argon Study: To determine whether argon blue-green laser photocoagulation of leaking abnormal blood vessels in choroidal neovascular membranes outside the fovea (200 to 2,500 microns from the center of the foveal avascular zone [FAZ]) is of benefit in preventing or delaying loss of central vision in patients with age-related (senile) macular degeneration (AMD), presumed ocular histoplasmosis (POH), and idiopathic neovascular membranes (INVM). A separate trial was conducted for each of the three underlying conditions. Krypton Study: To determine whether krypton red laser photocoagulation of choroidal neovascular lesions with the posterior border 1 to 199 microns from the center of the FAZ is of benefit in preventing or delaying large losses of visual acuity in patients with AMD, POH, and INVM. A separate trial was conducted for each of the three underlying conditions. Foveal Study: To determine whether laser photocoagulation is of benefit in preventing or delaying further visual acuity loss in patients with new (never treated) or recurrent (previously treated with laser photocoagulation) choroidal neovascularization under the center of the FAZ. Two separate trials, one for each type of lesion, were carried out. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000158 •

Multi-Ethnic Study of Atherosclerosis (MESA) - Ancillary Eye Study Condition(s): Atherosclerosis; Cardiovascular Diseases; Coronary Arteriosclerosis; Coronary Disease; Cerebrovascular Disorders; Heart Failure, Congestive; Myocardial Infarction; Heart Diseases; Diabetes Mellitus, non-insulin dependent; Hypertension; Diabetic Retinopathy; Macular Degeneration; Diabetes Mellitus Study Status: This study is no longer recruiting patients. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To evaluate the relation of retinal microvascular characteristics to subclinical cardiovascular disease, clinical disease, and their risk factors in the MultiEthnic Study of Atherosclerosis (MESA) cohort. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041444

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Phase 3 Study to evaluate Anecortave Acetate vs. Visudyne for the treatment of the wet form of AMD. Condition(s): Macular Degeneration Study Status: This study is no longer recruiting patients.

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Sponsor(s): Alcon Research Purpose - Excerpt: The purpose of this study is to demonstrate that Anecortave Acetate is as effective after twelve months of treatment as photodynamic therapy (PDT) with Visudyne in patients eligible for initial PDT treatment for wet age-related macular degeneration. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00041483 •

Randomized Trial of Beta-Carotene and Macular Degeneration Condition(s): Macular Degeneration Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether 50 mg of beta-carotene taken every other day reduces the risk of developing age-related macular degeneration (AMD) among male U.S. physicians who were aged 40 to 84 in 1982. To investigate the possible relationship of AMD with other antioxidants, including selenium and vitamins A, C, and E. To identify potential risk factors for development of AMD. Possible risk factors include height, systemic hypertension, cardiovascular disease, blood cholesterol, cigarette smoking, iris and skin color, sunlight exposure, body mass index, diabetes, and alcohol intake. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000152

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Randomized Trials of Vitamin Supplements and Eye Disease Condition(s): Macular Degeneration; Cataract Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether vitamin E supplementation reduces the risk of cataract and age-related macular degeneration (AMD) in women. To determine whether vitamin C supplementation reduces the risk of cataract and AMD in women. To determine whether beta-carotene supplementation reduces the risk of cataract and AMD in women. To determine whether alternate day, low-dose aspirin reduces the risk of cataract and AMD in women. To identify potential risk factors for cataract and AMD including cigarette smoking, alcohol intake, blood pressure, blood cholesterol, cardiovascular disease, height, body mass index, and diabetes. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000161

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Submacular Surgery Trials (SST) Condition(s): Macular Degeneration; Histoplasmosis Study Status: This study is no longer recruiting patients. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether surgical removal of subfoveal choroidal neovascularization (CNV) and associated hemorrhage in patients with age-related macular degeneration (AMD), the ocular histoplasmosis syndrome (OHS), or idiopathic CNV stabilizes or improves vision more often than observation. To determine how surgical removal compared to observation of subfoveal CNV due to AMD, OHS, or idiopathic causes changes the patient's perception of health- and vision-related "quality of life," as measured by telephone interview using the Medical Outcomes Survey Short Form-36 (MOS SF-36) instrument, the Hospital Anxiety and Depression Scale, and the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). To determine whether randomized trials of surgery are warranted for patients with subfoveal CNV associated with age-related macular degeneration not suitable for laser treatment. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000150

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Branch Vein Occlusion Study Condition(s): Hemorrhage

Macular

Degeneration;

Neovascularization,

Pathologic;

Vitreous

Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: To determine whether scatter argon laser photocoagulation can prevent the development of neovascularization. To determine whether peripheral scatter argon laser photocoagulation can prevent vitreous hemorrhage. To determine whether macular argon laser photocoagulation can improve visual acuity in eyes with macular edema reducing vision to 20/40 or worse. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00000162 •

Diabetic Retinopathy and Visual Function Study Condition(s): Diabetic Retinopathy; Macular Degeneration; Vision, Subnormal Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: The purpose of this study is to evaluate possible mechanisms of central visual loss in patients with diabetes mellitus. The visual loss of interest to be investigated is that associated with macular edema (prior to and following laser photocoagulation treatment) and that associated with panretinal photocoagulation. The evaluation will be performed with psychophysical testing, i.e., static perimetry and

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contrast sensitivity function. Of particular interest, the mechanisms of visual loss associated with macular edema (prior to and following laser photocoagulation) will be further investigated. Photoreceptor-mediated visual loss will be assessed by measurements of the Stiles-Crawford effect. Visual loss mediated by post-receptoral retinal changes will be assessed by measuring the Westheimer spatial desensitization/sensitization effect. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001346 •

Fluocinolone Implant to Treat Macular Degeneration Condition(s): Choroidal Neovascularization; Macular Degeneration Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will test the safety and effectiveness of a fluocinolone implant to treat age-related macular degeneration. This eye disease can severely impair central vision, affecting a person's ability to read, drive, and carry out daily activities. It is the leading cause of vision loss in people over age 60. The fluocinolone implant is a tiny plastic rod with a pellet of the steroid fluocinolone on the end. The pellet slowly dissolves and releases the medication into the fluid in the eye. Vision loss in macular degeneration is caused by the formation of new blood vessels in the choroid-a thin, pigmented vascular layer of the eye behind the retina. These abnormal vessels leak blood under the macula, the part of the retina that determines central vision. Tissue studies show evidence of inflammation in the retinas of patients. This study will test whether the slow release of the steroid fluocinolone directly into the affected part of the eye can prevent or slow further vision loss. Preliminary animal and human studies with fluocinolone implants have shown some benefit in reducing blood vessel growth and improving or stabilizing vision. Patients 50 years of age and older with age-related macular degeneration may be eligible for this study. Study patients will be randomly assigned to one of two treatment groups. One will receive a 0.5-mg dose implant; the other will receive a 2-mg dose implant. Theoretically, the implants can release the medicine for 2 to 3 years. Participants will have a medical history, physical examination and complete eye examination. The latter will include a vision test, eye pressure measurement, examination of the pupils, lens, retina, and eye movements. Photographs of the eye will be taken with a special camera. Patients will also undergo fluorescein angiography, a test that takes pictures of the retina using a yellow dye called sodium fluorescein. The dye is injected into the blood stream through a vein. After it reaches the blood vessels of the eye, photographs are taken of the retina. When the above tests are completed, patients will be scheduled for surgery to place the implant. The procedure will be done under either local or general anesthesia. Follow-up visits will be scheduled 1, 2, 4, and 6 weeks after surgery, then at 3 and 6 months after surgery, and then every 6 months until the implant is depleted of medicine or is removed. Several of the exams described above will be repeated during the follow-up period to evaluate the treatment and side effects, if any. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00008515

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Long Term Follow-Up of Diabetic Retinopathy Condition(s): Blindness; Cataract; Diabetes Mellitus; Diabetic Retinopathy; Macular Degeneration Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: The efficacy of laser photocoagulation treatment for diabetic retinopathy has been demonstrated by several National Eye Institute (NEI) sponsored clinical trials. The Diabetic Retinopathy Study (DRS) demonstrated that scatter photocoagulation reduces the risk of blindness from diabetic retinopathy. The Early Treatment Diabetic Retinopathy Study (ETDRS) extended these findings by providing information on when to initiate scatter photocoagulation and by demonstrating that focal treatment was effective in treating macula edema. The Krypton Argon Regression Neovascularization Study (KARNS) showed that scatter photocoagulation with krypton red laser was just as safe and effective as the argon blue-green laser in the treatment of proliferative diabetic retinopathy. Unfortunately, there is little data on the long term effects of photocoagulation on visual function. The first objective of this study is to assess the long term effects of photocoagulation for diabetic retinopathy. A second objective is to provide additional information on the risk of progression of cataracts in persons with diabetes. All patients previously treated with laser photocoagulation (focal and/or scatter) are eligible to participate in this long term study. The first priority will be given to patients who participated in the ETDRS and KARNS because of the wealth of information available regarding the details of their treatment and course after treatment. Study evaluations will include a standard ophthalmic examination, fluorescein angiography, lens and fundus photography. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001395

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Lutein for Age-Related Macular Degeneration Condition(s): Macular Degeneration Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: This study will examine whether taking the vitamin lutein changes lutein blood levels. Lutein, vitamin C, vitamin E and beta-carotene may be useful in treating the eye disease age-related macular degeneration, but more information is needed to support this. Age-related macular degeneration can significantly impair the ability to read, drive, and carry out daily activities. It is the most common cause of vision loss in people over age 60. Lutein a carotenoid that occurs naturally in the retina (the back part of the eye), especially the macula-the part of the retina that is important for fine, detailed vision. Men and women 60 years of age and older, with or without agerelated macular degeneration, may be eligible for this study. Candidates will undergo the following tests: 1. Medical history and physical examination. 2. Eye examinationIncludes evaluation of visual acuity, measurement of eye pressure, examination of the lens, retina, pupils and eye movements, and photographs of the eye. 3. Visual field study-Examines the ability to see objects in the periphery. The subject looks at a target on a screen and indicates when lights that appear in other places on the screen are visible. 4. Flicker photometry-The subject looks at a flashing light and turns a knob until

144 Macular Degeneration

the light stops flashing. 5. Blood tests-To measure blood levels of lutein and other carotenoids, liver function, cholesterol and triglycerides. Participants will be randomly assigned to take one of three dosages of lutein (2.5 milligrams, 5 milligrams or 10 milligrams) for 6 months and will be examined at follow-up visits scheduled 1, 3, 6, 9 and 12 months after starting lutein. During these visits, many of the exams described above will be repeated to evaluate the effects of lutein treatment on the eye. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006202 •

Phase I Study of Corticosteroid Treatment of Neovascularization in Age-related Macular Degeneration

Ill-defined

Choroidal

Condition(s): Choroidal Neovascularization; Macular Degeneration Study Status: This study is completed. Sponsor(s): National Eye Institute (NEI) Purpose - Excerpt: Age-related macular degeneration (AMD) represents the most common cause of blindness in patients over the age of 60. The major cause of vision loss in this disease is due to the development of choroidal neovascular membrane formation (CNVM). Several clinical trials have proven that eyes with "well-defined" CNVM or lesions that can be readily demarcated with fluorescein angiography can be successfully treated with laser photocoagulation. However, up to 87% of eyes present with "illdefined" CNVM or lesions that cannot be well demarcated on fluorescein angiography and are not amenable to laser photocoagulation. No beneficial treatment for this form of choroidal neovascularization has been established. Histopathologic study has demonstrated the presence of inflammatory and reparative responses in the retina of patients with ill-defined choroidal neovascularization. Since corticosteroids have been shown to downregulate many of the cellular factors involved in both inflammation and repair, the present study is designed to assess the ability of corticosteroid injection around the eye to prevent severe vision loss associated with "ill-defined" choroidal neovascularization in the setting of age-related macular degeneration. The study will be organized as a randomized open label control clinical trial involving 2 phases. Phase 1 involving 40 patients will establish the feasibility and safety of this treatment modality. Phase 2 will place emphasis on efficacy of the study. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001615 •

Phase II/III study of anti-VEGF in neovascular AMD Condition(s): Macular Degeneration; Choroidal Neovascularization Study Status: This study is completed. Sponsor(s): Eyetech Pharmaceuticals

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Purpose - Excerpt: The purpose of the study is to determine whether the anti-VEGF drug is effective at stabilizing and/or improving vision in patients with the wet form of AMD Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00021736

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “macular degeneration” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. PATENTS ON MACULAR DEGENERATION Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “macular degeneration” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on macular degeneration, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Macular Degeneration By performing a patent search focusing on macular degeneration, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on macular degeneration: •

.alpha.V integrin receptor antagonists Inventor(s): Duggan; Mark E. (Schwenksville, PA), Halczenko; Wasyl (Lansdale, PA), Hutchinson; John H. (Philadelphia, PA), Li; Aiwen (Audubon, PA), Meissner; Robert S. (Schwenksville, PA), Patane; Michael A. (Billerica, MA), Perkins; James J. (Churchville, PA), Steele; Thomas G. (Schwenksville, PA), Wang; Jiabing (Chalfont, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,472,403 Date filed: January 19, 2001 Abstract: The present invention relates to novel imidazolidinone derivatives thereof, their synthesis, and their use as.alpha.v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors.alpha.v.beta.3 and/or.alpha.v.beta.5 and are useful for inhibiting bone resorption, treating and preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammation, inflammatory arthritis, viral disease, cancer, and metastatic tumor growth. Excerpt(s): The present invention relates to imidazolidinone derivatives, their synthesis, and their use as.alpha.v integrin receptor antagonists. More particularly, the compounds of the present invention are antagonists of the integrin receptors.alpha.v.beta.3,.alpha.v.beta.5, and.alpha.v integrin receptors associated with other.beta.-subunits, and are useful for inhibiting bone resorption, treating and/or preventing osteoporosis, and inhibiting vascular restenosis, diabetic retinopathy, macular degeneration, angiogenesis, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth. It is believed that a wide variety of disease states and conditions can be mediated by acting on integrin receptors and that integrin receptor antagonists represent a useful class of drugs. Integrin receptors are heterodimeric transmembrane receptors through which cells attach and communicate with extracellular matrices and other cells. (See S. B. Rodan and G. A. Rodan, "Integrin Function In Osteoclasts," Journal of Endocrinology, 154: S47-S56 (1997), which is incorporated by reference herein in its entirety). In one aspect of the present invention, the compounds herein are useful for inhibiting bone resorption. Bone resorption is mediated by the action of cells known as osteoclasts. Osteoclasts are large multinucleated cells of up to about 400 mm in diameter that resorb mineralized tissue, chiefly calcium carbonate and calcium phosphate, in vertebrates. Osteoclasts are actively motile cells that migrate along the surface of bone, and can bind to bone, secrete necessary acids and proteases, thereby causing the actual resorption of mineralized tissue from the bone. More specifically, osteoclasts are believed to exist in at least two physiological states, namely, the secretory state and the migratory or motile state. In the secretory state, osteoclasts are flat, attach to the bone matrix via a tight attachment zone (sealing zone), become highly polarized, form a ruffled border, and secrete lysosomal enzymes and protons to resorb bone. The adhesion of osteoclasts to bone surfaces is an important initial step in bone resorption. In the migratory or motile state, the osteoclasts migrate across bone matrix and do not take part in resorption until they again attach to bone. Web site: http://www.delphion.com/details?pn=US06472403__

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Amine salts of an integrin receptor antagonist Inventor(s): Humphrey; Guy R. (Hillsborough, NJ), Waters; Marjorie See (Cranbury, NJ), Xu; Wei (North Wales, PA) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,444,680 Date filed: November 29, 2001 Abstract: Amine salts of 3-(2-methyl-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl) -nonanoic acid are potent antagonists of the integrin.alpha.v.beta.3 receptor and are useful for the prevention and/or treatment of osteoporosis and vascular restenosis, as well as conditions associated with excessive angiogenesis, such as macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth. The invention also relates to a process for the preparation of the novel salts as well as pharmaceutical compositions containing the salts and methods of using the salts. Also disclosed are 3(R)- and 3(S)-(2methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl )-nonanoic acid in the form of a zwitterion trihydrate. Excerpt(s): The present invention relates to particular salts of an integrin receptor antagonist. More particularly, the invention relates to amine salts of 3-(2-methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl) -nonanoic acid, which are potent integrin.alpha.sub.v.beta.sub.3 receptor antagonists. These novel salts are therefore useful for the treatment and prevention of diseases and conditions for which an antagonist of the integrin.alpha.sub.v.beta.sub.3 receptor is indicated. Integrin.alpha.sub.v.beta.sub.3 receptor antagonists have been described as being of use for the prevention and/or treatment of osteoporosis, vascular restenosis, macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth [see, for example, M. E. Duggan, et al., "Ligands to the integrin receptor.alpha.sub.v.beta.sub.3, Exp. Opin. Ther. Patents, 10: 1367-1383 (2000); M. Gowen, et al., "Emerging therapies for osteoporosis," Emerging Drugs, 5: 1-43 (2000); J. S. Kerr, et al., "Small molecule.alpha.sub.v integrin antagonists: novel anticancer agents," Exp. Opin. Invest. Drugs, 9: 1271-1291 (2000); and W. H. Miller, et al., "Identification and in vivo efficacy of small-molecule antagonists of integrin.alpha.sub.v.beta.sub.3 (the vitronectin receptor)," Drug Discovery Today, 5: 397-408 (2000)]. U.S. Pat. No. 6,048,861, assigned to Merck & Co., describes a class of 9-substituted-3-aryl-nonanoic acid derivatives, which are potent integrin.alpha.sub.v.beta.sub.3 receptor antagonists and therefore useful for inhibiting bone resorption, vascular restenosis, treating and/or preventing osteoporosis, and inhibiting diseases and conditions associated with excessive and undesirable angiogenesis. Specifically disclosed in U.S. Pat. No. 6,048,861 is 3-(2-methyl-pyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1, 8]-naphthyridin-2-yl)-nonanoic acid. Pharmaceutically acceptable salts of this compound are generically encompassed within the scope of U.S. Pat. No. 6,048,861. Web site: http://www.delphion.com/details?pn=US06444680__

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Device for the treatment of macular degeneration and other eye disorders Inventor(s): Schachar; Ronald A. (Dallas, TX) Assignee(s): RAS Holding Corp (Dallas, TX) Patent Number: 6,589,217 Date filed: November 26, 2001 Abstract: Introduced is a device that may be used to treat the effects of macular degeneration and other eye disorders by increasing the optical effect of the retinal surface of the eye. This may be accomplished using a device whose body has a shape prescribed to increase the depth of the fovea and, in the process, make the sides of the clivus more convex, thereby utilizing the varying optical properties of the retinal area. A suitable association of this device with the eye will cause an image beam traveling from the lens through the vitreous humor to magnify and impinge an image perception area encompassing the macula. According to one advantageous embodiment, the device includes a body adapted for association with the eye to manipulate the retina of the eye to effectively augment the photoreceptor cells proximate the macula of the eye. The body of the device may be that of a band, a segment, a partial band, a plate, or, for that matter, any shape suitably adapted to perform the functions described herein to treat the effects of macular degeneration as well as other eye disorders. Excerpt(s): which are commonly owned by the assignee of the present invention. The disclosures of these related United States patent applications and issued United States patents (collectively referred to hereafter as the "Presbyopia and Related Eye Disorder Patent Documents") are incorporated herein by reference for all purposes as if fully set forth herein. The present invention is generally related to the treatment of eye disorders and, more particularly, to device for the treatment of macular degeneration. Macular degeneration is a degenerative (age related) process that involves a highly specialized central part of the retina of the eye known as the macula, which is responsible for detailed central vision tasks such as reading, television viewing, sewing, etc. The various risk factors that may play a role in the cause of macular degeneration are being acutely studied--heredity, nutritional deficiencies, arteriosclerosis and hypertension, smoking, exposure to ultraviolet light, etc., are all suspect but further research is necessary to clearly identify the most significant factors. Web site: http://www.delphion.com/details?pn=US06589217__

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Eyeglasses and method of making same for the treatment of low-vision Inventor(s): Alberts; Davida Charlene (1124 Reedsport Pl., DeSoto, TX 75115) Assignee(s): none reported Patent Number: 6,488,374 Date filed: February 12, 2002 Abstract: Eyeglasses for the treatment of low-vision and macular degeneration include a frame for supporting lenses on an occipital dexter side and an occipital sinister side. An occipital dexter lens has a near portion and a distance portion. The near portion has a dioptric power for near vision in a right eye, and the distance portion has a dioptric power for distance vision in the right eye. The optical center of the near portion of the occipital dexter lens is below and on the temporal side of the optical center of the distance portion. An occipital sinister lens similarly has a near portion and a distance

Patents 151

portion. The near portion has a dioptric power for near vision in a left eye, and the distance portion has a dioptric power for distance vision in the left eye. The optical center of the near portion of the occipital sinister lens is below and on the temporal side of the optical center of the distance portion. Excerpt(s): The present invention is directed to an ophthalmic apparatus, and in particular to bifocal eyeglasses for the treatment of patients with low-vision, and more particularly macular degeneration. The macula is the small center portion of the light sensitive retina, which is the lining at the back of the eye. Light rays from objects come to a focus in the eye on the retina and are converted to electrical impulses that are interpreted by the brain. The macula is responsible for sharp, straight-ahead vision, which is necessary for functions such as reading, driving, and recognizing faces. Macular degeneration is a disorder that affects the macula causing decreased visual acuity and possible loss of central vision. The degeneration results from a partial breakdown of the retinal pigment epithelium (RPE). Breakdown of the RPE interferes with the metabolism of the retina, causing thinning of the retina (the "dry" phase of macular degeneration] and may allow these harmful elements from the blood to damage and scar the retina [the "wet" phase of macular degeneration]. Web site: http://www.delphion.com/details?pn=US06488374__ •

Eyesight enhanced maintenance composition Inventor(s): Gorsek; Wayne F. (Boynton Beach, FL) Assignee(s): Vitacost.com, Inc. (Boynton Beach, FL) Patent Number: 6,649,195 Date filed: July 11, 2002 Abstract: A powerful formulation for preventing and treating macular degeneration, cataracts, glaucoma and other eye diseases, and contains over thirty naturally effective vitamins, minerals, phytonutrients and amino acids, which have all been found to demonstrate a powerful protective effect on the health of the eye. Excerpt(s): The invention relates to a composition for maintaining healthy eyesight. The composition provides over thirty naturally effective vitamins, minerals, phytonutrients and amino acids, which have all been found to demonstrate a powerful protective effect on the health of the eye. Vision loss is often related to damage caused by free radicals. A free radical is a highly reactive molecule that binds to and destroys body components. Free radicals are found in every thing from air pollution and chemicals in the water we drink, to preservatives in the foods we eat and cigarette smoke. As a result of their dependence on light to function properly, the eyes are especially vulnerable to free radical attacks. Paradoxically, while this light enables a person to see, it also creates additional free radicals that lead to cell and membrane damage. Web site: http://www.delphion.com/details?pn=US06649195__

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Gene therapy for inhibition of angiogenesis Inventor(s): Bett; Andrew J. (Lansdale, PA), Goldman; Corey K. (Birmingham, AL), Huckle; William R. (Lansdale, PA), Kendall; Richard L. (Doylestown, PA), Thomas, Jr.; Kenneth A. (Chatham Borough, NJ) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 6,375,929 Date filed: October 26, 1999 Abstract: The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with solid tumor growth, tumor metastasis, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration Gene therapy methodology is disclosed for inhibition of primary tumor growth and metastasis by gene transfer of a nucleotide sequence encoding a soluble form of a VEGF tyrosine kinase receptor to a mammalian host. The transferred nucleotide sequence transcribes mRNA and a soluble receptor protein which binds to VEGF in extracellular regions adjacent to the primary tumor and vascular endothelial cells. Formation of a sVEGF-R/VEGF complex will prevent binding of VEGF to the KDR and FLT-1 tyrosine kinase receptors, antagonizing transduction of the normal intracellular signals associated with vascular endothelial cell-induced tumor angiogenesis. In addition, expression of a soluble receptor tyrosine kinase may also impart a therapeutic effect by binding either with or without VEGFs to form nonfunctional heterodimers with full-length VEGF-specific tyrosine kinase receptors and thereby inhibiting the mitogenic and angiogenic activities of VEGFs. Excerpt(s): The present invention relates to methods of gene therapy for inhibiting angiogenesis associated with tumor growth, inflammation, psoriasis, rheumatoid arthritis, hemangiomas, diabetic retinopathy, angiofibromas, and macular degeneration. This invention also relates to animal models useful in the investigation of gene therapymediated inhibition of angiogenesis. The invention also relates to recombinant vectors which are useful in the disclosed gene therapy methods. Vascular endothelial cells form a luminal non-thrombogenic monolayer throughout the vascular system. Mitogens promote embryonic vascular development, growth, repair and angiogenesis in these cells. Angiogenesis involves the proteolytic degradation of the basement membrane on which endothelial cells reside followed by the subsequent chemotactic migration and mitosis of these cells to support sustained growth of a new capillary shoot. One class of mitogens selective for vascular endothelial cells include vascular endothelial growth factor (referred to as VEGF or VEGF-A) and the homologues placenta growth factor (PlGF), VEGF-B and VEGF-C. Web site: http://www.delphion.com/details?pn=US06375929__

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Integrin antagonists Inventor(s): Jadhav; Prabhakar K. (Wilmington, DE), Pitts; William J. (Newtown, PA) Assignee(s): Bristol - Meyers Squibb Pharma Company (Princeton, NJ) Patent Number: 6,489,333 Date filed: April 9, 2001 Abstract: This invention relates to novel heterocycles which are useful as antagonists of the.alpha.sub.v.beta.sub.3 integrin, the.alpha.sub.2b.beta.sub.3 integrin, and related cell

Patents 153

surface adhesive protein receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion, the treatment of angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, thrombosis, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis. Excerpt(s): Angiogenesis or neovascularization is critical for normal physiological processes such as embryonic development and wound repair (Folkman and Shing, J. Biol. Chem. 1992, 267:10931-10934; D'Amore and Thompson, Ann. Rev. Physiol. 1987, 49:453-464). However, angiogenesis also occurs pathologically, for example, in ocular neovascularization (leading to diabetic retinopathy, neovascular glaucoma, retinal vein occlusion and blindness), in rheumatoid arthritis and in solid tumors (Folkman and Shing, J. Biol. Chem., 1992, 267:10931-10934; Blood and Zetter, Biochim. Biophys. Acta., 1990, 1032:118-128). Tumor dissemination, or metastasis, involves several distinct and complementary components, including the penetration and transversion of tumor cells through basement membranes and the establishment of self-sustaining tumor foci in diverse organ systems. To this end, the development and proliferation of new blood vessels, or angiogenesis, is critical to tumor survival. Without neovascularization, tumor cells lack the nourishment to divide and will not be able to leave the primary tumor site (Folkman and Shing, J. Biol. Chem., 1992, 267:10931-10934). Web site: http://www.delphion.com/details?pn=US06489333__ •

Mesozeaxanthin formulations for treatment of retinal disorders Inventor(s): Bone; Richard A. (Miami, FL), Howard; Alan Norman (Cambridge, GB), Landrum; John T. (Miami, FL) Assignee(s): The Howard Foundation (Cambridge, GB) Patent Number: 6,329,432 Date filed: March 2, 2001 Abstract: Meso-zeaxanthin compositions for pharmaceutical use and use of mesozeaxanthin to increase the deposition of macular pigment in the human eye, and for the therapeutic treatment or prophylaxis of diseases and disorders of the macula, in particular age-related macular degeneration (AMD). Excerpt(s): The invention relates to the use of meso-zeaxanthin to increase the deposition of macular pigment in the human eye, and for the therapeutic treatment or prophylaxis of diseases and disorders of the macula, and in particular age-related macular degeneration (AMD). The macula is the anatomical region of the retina which in man is responsible for central vision. Centered on the fovea, where the visual axis meets the retina, it extends radially outwards to a distance of about 2.75 mm (Davson, 1990). The macula is divided into the inner macula and the outer macula. The inner macula extends radially out to a distance of 1.5 mm while the outer macula is defined by the surrounding annular ring. The central portion of the macula is easily recognizable because of its yellow coloration which results from the presence of macular pigment. Despite its small size, the macula is endowed with the highest degree of visual acuity. It is therefore not surprising that considerable effort is devoted to understanding and, when possible, treating diseases which disrupt the nominal functioning of the macula. One such disease is age-related macular degeneration (AMD) which occurs in about

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20% of the population above the age of 65 and is the leading cause of visual impairment in the USA and UK. AMD has up to the present time been an irreversible condition. Web site: http://www.delphion.com/details?pn=US06329432__ •

Method and compositions for treatment of the aging eye Inventor(s): Petrus; Edward J. (Austin, TX) Assignee(s): Advanced Medical Instruments (Austin, TX) Patent Number: 6,573,299 Date filed: September 20, 1999 Abstract: This invention relates to a method for the prevention and treatment of orbital disorders associated with the aging eye in mammals by the application of a topical composition comprising a permeation enhancing amount of one or more penetration enhancers, and one or more bio-affecting agents which penetrate into the underlying tissues and into the vascular network of the orbit. Another object of this invention is the improvement of age-related changes to the eyelids such as dry skin, wrinkles, keratoses, age spots and pigmented skin lesions. It is a further object of this invention to prevent and treat cataract formation, glaucoma, diabetic retinopathy and macular degeneration. Excerpt(s): A method and compositions for the prevention and treatment of orbital disorders associated with the aging eye. The eyes, usually the very first aspect noticed of a person's face, often show the earliest signs of the aging process. The aging process is ordinary first demonstrated by wrinkles of the eyelids, the need for glasses to correct for presbyopia, or visual loss associated with cataracts, glaucoma, diabetic retinopathy or macular degeneration. Eyelids show age-related changes such as dry skin, wrinkles, keratoses, age spots and pigmented skin lesions. Dry eyelid skin appears dull and loses its radiance and is usually caused by low humidity, cold weather, contact pressure, detergents, solvents and some chemicals. A moisturizing topical lotion, cream or ointment usually restores the dry skin condition of the eyelids. Web site: http://www.delphion.com/details?pn=US06573299__

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Method for increasing intestinal absorption of fat soluble vitamins in postmenopausal women and lower animals Inventor(s): Gross; Kathy Lynn (Topeka, KS), Koo; Sung I. (Manhattan, KS), Owen; Kevin (Manhattan, KS) Assignee(s): Hill's Pet Nutrition (Topeka, KS), Kansas State Research Foundation (Manhattan, KS), Lonza Ltd. (Basel, CH) Patent Number: 6,476,010 Date filed: March 1, 2001 Abstract: The present invention provides a method for increasing the intestinal (lymphatic) absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman. The method comprises orally administering to a post-menopausal woman in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of Lcarnitine. The L-carnitine enhances the antioxidant defense mechanism and lowers the risk of certain degenerative diseases, such as coronary heart disease, age-related

Patents 155

macular degeneration, osteoporosis, cancer, and Alzheimer's, in post-menopausal women. The invention also provides a method for increasing the intestinal absorption of a fat soluble vitamin in an animal. The method comprises orally administering to the animal in need thereof, a fat soluble vitamin and a fat soluble vitamin absorption increasing effective amount of L-carnitine. Excerpt(s): This invention relates to a method for increasing the intestinal absorption, cellular concentration, biliary secretion, hepatic storage, and/or liver concentration of a fat soluble vitamin in a post-menopausal woman or a lower animal by orally administering L-carnitine and a fat soluble vitamin. L-carnitine plays a crucial role in the energy supply of tissues by modulating the entry of long-chain fatty acids into the mitochondrial matrix and their subsequent oxidation. Consistent with such a metabolic role, L-carnitine has been shown to be effective in lowering the serum levels of cholesterol, triglyceride, and free fatty acids, while increasing high density lipoprotein (HDL) cholesterol which is antiatherogenic. See Pola, P. et al., "Carnitine in the theraphy of dyslipemic patients", Curr Ther Res 27:208-16 (1980); Lacour, B. et al., "Carnitine improves lipid abnormalies in haemodialysis patients", Lancet 12:763-4 (1980); Avogaro, P., "Acute effect of L-carnitine on FFA and beta-hydroxy-butyrate in man", Pharmacol Res Commun 13:433-50 (1981); and Vacha, G. M. et al. "Favourable effects of L-carnitine treatment on hypertriglyceridemia in hemodialysis patients: Decisive role of low levels of high density lipoprotein cholesterol", Am J Clin Nutr 38:532-40 (1983). Existing evidence indicates that L-carnitine and its esters enhance the stability and integrity of erythrocyte membranes by participating in the reacylation (repair) of membrane phospholipids subjected to oxidative damage. See Arduini, A. et al., "Effect of propionyl-L-carnitine treatment on membrane phospholipid fatty acid turnover in diabetic rat erythrocytes", Mol Cell Biochem 152:31-7 (1995); Arduini, A. et al., "Carnitine palmitoyltransferase and acyl-CoA binding protein: two more players in the membrane phospholipid fatty acid turnover of human red cells?", Biochem J 325:811-4 (1997); and Arduini, A. et al., "Addition of L-carnitine to additive solution-suspended red cells stored at 4.degree. C. reduces in vitro hemolysis and improves in vivo viability", Trandfusion 37:166-74 (1997). It is of interest to note that such an action of L-carnitine and its esters is shown in the erythrocyte devoid of mitochondrial. L-carnitine supplementation to old rats has been shown to reverse the age-related decline in mitochondrial function, which may be linked to the membrane-stabilizing effect of Lcarnitine. See Hagen, T. M. et al., "Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity", Proc Natl Acad Sci USA 95:9562-6 (1998). This finding is of particular significance in that oxidative damage to mitochondrial DNA increases markedly with age, leading to impaired cellular metabolism and function. See Hagen, T. M. et al., "Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase", Proc Natl Acad Sci USA 94:3064-9 (1997). Postmenopausal women make up over 15% of the total population in industrialized countries. By 2030, the proportion of postmenopausal women is predicted to increase to 23% of the total population. See Hill, K., "The demography of menopause", Maturitas 23:113-127 (1996). In addition, numerous epidemiological studies have shown that depletion of estrogen at the menopause influences cause-specific morbidity and mortality in later life. From the nutritional standpoint, the menopause is the time when the body's ability to absorb, assimilate, and metabolize nutrients begins to deteriorate. Consequently, the body status of nutrients is compromised at and after menopause, with the manifestations of specific nutrient deficiency symptoms with time. Web site: http://www.delphion.com/details?pn=US06476010__

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Method of ocular treatment Inventor(s): Grinstead; Robert (206 Hector Ave., Metairie, LA 70005), Khoobehi; Bahram (5024 Cleveland Pl., Metairie, LA 70003), Peyman; Gholam (8654 Pontchartrain Blvd., Unit #1, New Orleans, LA 70124) Assignee(s): none reported Patent Number: 6,524,330 Date filed: October 27, 2000 Abstract: A method for treating abnormal blood vessel growth and proliferation is disclosed. Members of the hypocrellin class of compounds such as hypocrellin A, hypocrellin B, and/or amino-substituted derivatives of hypocrellin B are administered and photoactivated with photodynamic therapy. The method may be used, for example, to treat ocular blood vessel proliferation as occurs with macular degeneration. Excerpt(s): This invention relates to a composition and method to treat abnormal blood vessel proliferation in the eye. Many therapeutic treatments of pathological conditions involve selective targeting of specific tissues or cells for destruction. For example, a goal in cancer therapy is to destroy only malignant cells while leaving normal cells undisturbed. As another example, a goal in ophthalmology is to destroy new abnormal blood vessels in the eye that can result in visual impairment if allowed to proliferate, while leaving normal existing blood vessels intact. In the mammalian eye, macular degeneration (also called age related macula degeneration, AMD) is a pathological condition that results in proliferation of new blood vessels in the subretinal area. The new blood vessels proliferate from the choriocapillaris through defects in Bruch's membrane beneath or on top of retinal pigment epithelium (RPE), and form vascular membranes. While the presence of the new vessels themselves is not problematic, new vessels leak blood and other serous fluid which accumulate in surrounding spaces. It is this fluid accumulation that leads to visual impairment. For example, in the retina, both the large vessels and the capillaries normally have intact vessel walls. In the choroid, the large vessels normally have intact vessel walls, but the capillary walls or membranes contain fenestrations or openings. Any endogenous or exogenous fluid present in these capillaries, for example, blood, serous fluid, solubilized drug, etc. will leak outside the vessels and into the surrounding area. The accumulation of fluid can result in serous and hemorrhagic detachment of the RPE and neurosensory retina, and can lead to loss of vision due to fibrous deform scarring. More than 90% of cases having significant loss of central vision in AMD are attributed to choroidal neovascularization and the resulting exudation and scarring. Choroidal neovascularization occurs in about 8-10% of all patients with AMD, and is also seen in patient with pathologic myopia and presumed ocular histoplasmosis syndrome, as well as other idiopathic conditions. Web site: http://www.delphion.com/details?pn=US06524330__

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Method of preventing proliferation of retinal pigment epithelium by retinoic acid receptor agonists Inventor(s): Campochiaro; Peter A. (Baltimore, MD), Chandraratna; Roshantha A. (Laguna Hills, CA), De Juan, Jr.; Eugene (Phoenix, MD), Nagpal; Sunil (Lake Forest, CA), Wheeler; Larry A. (Irvine, CA) Assignee(s): Allergan (Irvine, CA), The Johns Hopkins University School of Medicine (Baltimore, MD) Patent Number: 6,372,753 Date filed: March 27, 2000 Abstract: Proliferation of retinal pigment epithelium following surgery or trauma or resulting in ocular diseases associated with choroidal neovascularization, such as age related macular degeneration and histoplasmosis syndrome, is prevented by contacting retinal pigment epithelium cells with a therapeutic amount of a retinoic acid receptor (RAR agonist, preferably one with specific activity for retinoic acid receptors. Preferably the RAR agonist is also a potent antagonist of AP1-dependent gene expression. Alternatively, the proliferation of retinal pigment epithelium is ameliorated with a therapeutic amount of an AP-1 antagonist, alone or in combination with an RAR agonist. The drug can be administered by bolus injection into the vitreous cavity using a dosage from about 50 to 150.mu.g. Or by slow release from liposomes or an oil tamponade injected into the vitreous cavity. Formulations for preventing proliferation of retinal pigment epithelium are also provided. Excerpt(s): This invention relates to pharmacological uses of retinoids. More particularly, this invention relates to use of retinoids in treatment of ocular disorders. The retinal pigment epithelium (RPE) forms a monolayer of cells beneath the sensory retina that is normally mitotically inactive except when it is participating in retinal wound repair, in which it plays a central role. When wound repair is complete, the RPE usually stops proliferating; failure to do so can result in blinding disorders such as proliferative vitreoretinopathy (PVR) and disciform scarring. For instance, after detachment of the sensory retina, the RPE changes in morphology and begins to proliferate. Multilayered colonies of dedifferentiated RPE cells are formed. Cells then begin to migrate into the subretinal space where they engulf rod outer segments. In some instances cells migrate onto the surface of the retina and form epiretinal membranes. These events have been implicated in the pathogenesis of proliferative vitreoretinopathy, severe scarring occurring in association with macular degeneration, and poor or delayed recovery of vision after retinal reattachment. Age-related macular degeneration (AMD) is the major cause of blindness in patients over the age of 60 in the United States. Severe loss of vision in patients with AMD is usually due to the development of choroidal neovascularization (CNV). Laser treatment can ablate CNV and help to preserve vision in selected cases not involving the center of the retina; however, the treatment benefit is often transient due to the high rate of recurrent CNV (50% over 3 years and approximately 60% at 5 years) (Macular Photocoagulation Study Group, Arch. Ophthalmol. 204: 694-701, 1986). In addition, many patients who develop CNV are not good candidates for laser therapy because the CNV is too large for laser treatment, or the location cannot be determined so that the physician cannot accurately aim the laser. Web site: http://www.delphion.com/details?pn=US06372753__

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Methods for treating acromegaly and giantism with growth hormone antagonists Inventor(s): Chen; Wen Y. (Athens, OH), Kopchick; John J. (Athens, OH) Assignee(s): Ohio University/Edison Biotechnology Institute (Athens, OH) Patent Number: 6,583,115 Date filed: June 7, 1995 Abstract: The present invention relates to antagonists of vertebrate growth hormones obtained by mutation of the third alpha helix of such proteins (especially bovine or human GHs). These mutants-have growth-inhibitory or other GH-antagonizing effects. These novel hormones may be administered exogenously to animals, or transgenic animals may be made that express the antagonist. Animals have been made which exhibited a reduced growth phenotype. The invention also describes methods of treating acromegaly, gigantism, cancer, diabetes, vascular eye diseases (diabetic retinopathy, retinopathy of prematurity, age-related macular degeneration, retinopathy of sickle-cell anemia, etc.) as well as nephropathy and other diseases, by administering an effective amount of a growth hormone antagonist. The invention also provides pharmaceutical formulations comprising one or more growth hormone antagonists. Excerpt(s): This invention relates to novel muteins of growth hormone ("GH"), especially human growth hormone ("hGH"), which diminish, decrease or inhibit the growth of animals or otherwise diminish, decrease or inhibit the effects of endogenous GH by acting as an antagonist to growth hormone receptors ("GHRs"). This invention also relates to DNAs encoding such muteins as well as methods for the treatment of diseases and disorders that are wholly or partially mediated by GHRs using a GH antagonist. Several forms of mature bGH have been found in nature. The amino-terminus can vary (due to variation in the site of cleavage during secretion) so that the mature protein begins with either NH.sub.2 -Ala-Phe-Pro or NH.sub.2 -Phe-Pro, the latter referred to as "(des Ala) bGH". Additionally, the amino acid at bGH position 126 may be either Leu or Val, apparently as a result of allelic variation in the bovine population. Exogenous administration of bGH to cattle increases milk production, feed efficiency, growth rate, and the lean-to-fat ratio, and decreases fattening time. Web site: http://www.delphion.com/details?pn=US06583115__

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Methods for treating conditions and illnesses associated with abnormal vasculature Inventor(s): Alam; Abu (Lake Forest, IL), Flower; Robert W. (Hunt Valley, MD) Assignee(s): Akorn, Inc. (Buffalo Grove, IL) Patent Number: 6,443,976 Date filed: November 30, 1999 Abstract: Use of radiation-absorbing dyes (e.g., indocyanine green (ICG), fluorescein, rose bengal) and photodynamic dyes (e.g., hematoporphyrins, aminolevulinic acids, porphyrins, merocyanines, porphycenes, porfimer sodium, verteporfin, Photofrin II, PH-10, chlorins, zinc phthalocyanine, purpurins, pheophorbides, monoclonal antibodydye conjugates of any of the foregoing dyes) for the treatment of conditions associated with abnormal vasculature, including, generally, lesions, and, more specifically, tumors (cancerous and benign) and choroidal neovascularization (CNV) associated with agerelated macular degeneration (ARMD).

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Excerpt(s): The present invention relates generally to methods for treating harmful conditions and illnesses associated with abnormal vasculature. Abnormal vasculature in a body is typically associated with a lesion. Lesions are generally defined as an abnormal tissue structure located in an organ or other body part, and are often a manifestation of a harmful condition, disease or illness. Lesions may take many specific forms, e.g., choroidal neovascularization (CNV) found in the eye, and tumors, both benign and malignant, located in organs and other parts of the body. Common methods of treating abnormal vasculature use laser technology. One example of such methods, used in the treatment of CNV, is photodynamic therapy (PDT). The object of PDT is to permit selective destruction of undesirable tissue without damaging surrounding healthy tissue. This is possible because the photodynamic dyes used in PDT are selectively retained in the area to be treated. For example, in the case of CNV, the photodynamic dye selectively binds to the proliferating endothelium in the CNV. Similarly, in the case of tumors, the photodynamic dye remains in cancer cells for a longer period of time than in normal, healthy cells. Thus, only a general identification of the tissue to be treated need be obtained before administering PDT. Web site: http://www.delphion.com/details?pn=US06443976__ •

Methods of ophthalmic administration Inventor(s): Bowman; Lyle M. (Pleasanton, CA), Clark; Leslie A. (Alameda, CA), Hecker; Karl L. (Keene, NH), Pfeiffer; James F. (Oakland, CA) Assignee(s): InSite Vision, Incorporated (Alameda, CA) Patent Number: 6,378,526 Date filed: August 3, 1998 Abstract: Intrascleral injection of a therapeutic or diagnostic material at a location overlying the retina provides a minimally invasive technique for delivering the agent to the posterior segment of the eye. The procedure also allows for close proximity of the material to the targeted site and can be effectively used to treat conditions associated with the posterior segment of the eye, including macular degeneration, vein occlusion, and diabetic retinopathy. Excerpt(s): The present invention relates to methods of ophthalmic administration. Specifically, the methods relate to intrascleral injection of therapeutic or diagnostic materials. Delivering therapeutic or diagnostic agents to the posterior segment of the eye, especially to the retina, macula, etc., poses several challenges. Topical instillation of an agent to the front of the eye such as by eye drops, generally provides low amounts of the agent (including none) to the posterior portion of the eye, due in part to poor diffusion through the various layers as well as the natural clearing processes encountered. Providing effective amounts of an agent to, for example, the retina via topical instillation is generally not possible given the distance and number of layers between the deposit site of the agent and the site to be treated. Another potential shortcoming with topical instillation is that the composition tends to be quickly removed from the eye by tears and other natural clearing processes. The resulting short duration of contact can further limit the likelihood of an appreciable amount of the agent reaching the posterior segment. Conversely, systemic delivery of an agent to the posterior segment of the eye such as by oral administration, is limited by the bloodretinal barrier. The barrier limits the size and amount of agents that can reach the choroid and retina. Moreover, because the agent is systemically delivered, the dosage is limited so as not to provide a toxic dose of the agent to other parts of the body. This is

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especially a concern in treating chronic disorders where a long term dosing regimen is typically required. For this reason, overcoming the barrier by administering higher doses of the agent is usually not a practical alternative. Likewise, the risk of side effects is increased with systemic delivery. Web site: http://www.delphion.com/details?pn=US06378526__ •

Mouse model for ocular neovascularization Inventor(s): Campochiaro; Peter A. (Baltimore, MD), Zack; Donald J. (Lutherville, MD) Assignee(s): The Johns Hopkins University (Baltimore, MD) Patent Number: 6,479,729 Date filed: June 5, 2000 Abstract: Transgenic mammals are provided which develop neovascularization of the retina, similar to that found in a variety of disease states, including diabetes, age related macular degeneration, retinopathy of prematurity, sickle cell retinopathy. These mammals can be used as test systems to evaluate potential prophylactic and therapeutic regimens. The effect of a regimen on the neovascularization is indicative of its beneficial effect in a disease state which is associated with neovascularization. Excerpt(s): This invention is related to the field of retinopathies, particularly those caused by neovascularization. New blood vessel formation or neovascularization (NV) is essential for normal eye development, but it can also cause severe ocular disease. In the retina, NV is associated with a number of disease processes, the most common of which is diabetic retinopathy, a major cause of new blindness in developed nations.sup.1. Occlusion of retinal vessels leading to retinal ischemia is a feature shared by most diseases in which retinal NV occurs. This observation led to the hypothesis that the development of retinal NV is stimulated by one or more angiogenesis factors released by ischemic retina.sup.2, 3. Substantial effort has been devoted to identifying the factor or factors involved. The demonstration that vascular endothelial cell growth factor (VEGF) is upregulated by hypoxia.sup.4, 5 and that levels of VEGF are increased in the retina and vitreous of patients.sup.6-9 or laboratory animals.sup.10, 11 with ischemic retinopathies has focused attention on VEGF as a potential mediator of retinal angiogenesis. This is supported by studies showing that VEGF antagonists partially inhibit retinal or iris NV in animal models.sup.12-14. There is also ample-data indicating that VEGF can stimulate NV in other tissues.sup.15-18. Web site: http://www.delphion.com/details?pn=US06479729__

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Neural retinal cells and retinal pigment epithelium cells and their use in treatment of retinal disorders Inventor(s): Edge; Albert (Cambridge, MA) Assignee(s): Diacrin, Inc. (Charlestown, MA) Patent Number: 6,517,833 Date filed: June 12, 2001 Abstract: Compositions comprising porcine retinal cells and methods for using the compositions to treat retinal disorders are described. The porcine retinal cells are preferably fetal neural retina cells or retinal pigment epithelial cells. The porcine retinal

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cells can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine retinal cells can be modified such that an antigen (e.g., an MHC class I antigen) on the cell surface which is capable of stimulating an immune response against the cell in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cell when introduced into the subject. In one embodiment, the porcine retinal cells are obtained from a pig predetermined to be free from organisms which originate in pig and which are capable of transmitting infection or disease to the recipient subject. The porcine retinal cells of the present invention can be used to treat a xenogeneic subject having a retinal disorder (e.g., a human with retinis pigmentosa, light damaged retina and macular degeneration by introducing the cells into the retina of the subject. Excerpt(s): Macular degeneration is a disease of the retina which affects over thirteen million people in the United States and is characterized by loss of central vision due to the loss of photoreceptors in the central part of the retina, the macula lutea. D'Amico et al. (1994) New England J. Med. 331:95-106 and Kliffen et al. (1997) Microscopy Res. & Techniq. 36:106-122. The macula is the most important part of the eye for high resolution vision because there is a greater concentration of cone type photoreceptors which are responsible for color vision and visual acuity. Photoreceptor cells, especially rod cells, renew their outer segments at a high rate. Thus, as new lamellae discs are formed and added to the photoreceptor cells, the older lamellae discs at the tip are discarded. Retinal pigment epithelial (RPE) cells function to provide support for the retinal photoreceptors and are responsible for the metabolic digestion of the discarded outer segments of the neural retina. Thus, RPE cells are responsible for the phagocytosis and digestion of the discarded discs at a turn over rate of approximately 30-100 discs each day. Underlying the RPE cells is the choriocapillaris which contains the vasculature to provide nutrients and remove metabolic by-products from the retina. In macular degeneration, the RPE cells are dysfunctional, thereby leading to a build up of metabolic by-products, including discarded discs in the retina. The presence of metabolic debris and excess fluid in the retina damage photoreceptor cells, thereby compromising visual acuity. Cingle et al. (1996) Curr. Eye. Res. 15:433-438 and Curcio et al. (1996) Invest. Ophthal. & Vis. Sci. 37:1236-1249. In addition, the degeneration of the RPE layer is also reflected by ensuing atrophy of the choriocapillaris. Web site: http://www.delphion.com/details?pn=US06517833__ •

Ophthalmic brachytherapy device Inventor(s): Finger; Paul T. (1 Gracie Ter., Apt. 12A, New York, NY 10028) Assignee(s): none reported Patent Number: 6,443,881 Date filed: June 6, 2000 Abstract: A method and apparatus are provided for use in ocular brachytherapy. The device comprises a handle, an applicator coupled with said handle, and adapted to receive a source of radiation. The applicator is movable between a radiation shielding position and a position wherein radiation is allowed to reach the diseased area. A plurality of light-emitting diodes are located so as to define the area to be treated. A shield receives the applicator so as to shield the radiation source during insertion and positioning proximal the treatment site. An actuator moves the applicator between the shielded position and the treatment position. The method of treating macular degeneration employs the device according to the invention.

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Excerpt(s): The present invention relates generally to a device and method for the treatment of ocular diseases with radiation. Particularly, the device and method will be utilized to deliver a dose of radiation to a portion of the eye globe to treat subretinal neovascularization associated with age-related macular degeneration. Macular degeneration is a pathologic process associated with subretinal neovascularization. The subretinal neovascularization allows fluid, blood, and lipids to leak beneath the surface of the retina. This leakage has detrimental effects on the health of the globe. For example, this leakage may cause hypoxia, retinal detachment or other eye condition problems. These conditions can cause scarring that will destroy the macular retina. The effect of the scarring on the macular retina can be severe. Specifically, it may cause irreversible loss of central vision. There are currently two methods for treatment of macular degeneration. These methods utilize lasers to effect closure of subretinal neovascularization. While laser/photocoagulation is effective in closing subretinal neovascularization and preserving visual acuity, laser treatment is only effective in a small subset of patients, and can cause destruction of the overlying retina. The. other laser-assisted treatment utilizes light-activated dyes to close the subretinal neovascular vessels. Web site: http://www.delphion.com/details?pn=US06443881__ •

Regulated angiogenesis genes and polypeptides Inventor(s): Jay; Gilbert (North Bethesda, MD), Li; Xuan (Silver Spring, MD), Sun; Zairen (Rockville, MD) Assignee(s): Origene Technologies, Inc. (Rockville, MD) Patent Number: 6,657,054 Date filed: June 10, 2002 Excerpt(s): The present invention relates to all facets of novel polynucleotides, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are expressed in angiogenesis and are therefore useful in variety of ways, including, but not limited to, as molecular markers for blood vessels and blood vessel formation, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing, treating, and/or determining predisposition to diseases and conditions of the vascular system. The identification of specific genes, and groups of genes, expressed in pathways physiologically relevant to angiogenesis permits the definition of functional and disease pathways, and the delineation of targets in these pathways which are useful in diagnostic, therapeutic, and clinical applications. The present invention also relates to methods of using the polynucleotides and related products (proteins, antibodies, etc.) in business and computer-related methods, e.g., advertising, displaying, offering, selling, etc., such products for sale, commercial use, licensing, etc. Angiogenesis, the process of blood vessel formation, is a key event in many physiological processes that underlie normal and diseased tissue function. During ontogeny, angiogenesis is necessary to establish to the network of blood vessels required for normal cell, tissue and organ development and maintenance. In the adult organism, the production of new blood vessels is needed for organ homeostasis, e.g., in the cycling of the female endometrium, for blood vessel maturation during wound healing, and other processes involved in the maintenance of organism integrity. It also is important in regenerative medicine, including, e.g., in promoting tissue repair, tissue engineering, and the growth of new

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tissues, inside and outside the body. Not all angiogenesis is beneficial. Inappropriate and ectopic expression of angiogenesis can be deleterious to an organism. A number of pathological conditions are associated with the growth of extraneous blood vessels. These include, e.g., diabetic retinopathy, neovascular glaucoma, psoriasis, retrolental fibroplasias, angiofibroma, inflammation, etc. In addition, the increased blood supply associated with cancerous and neoplastic tissue, encourages growth, leading to rapid tumor enlargement and metastasis. Web site: http://www.delphion.com/details?pn=US06657054__ •

Synthesis and clinical uses of D,.alpha.-tocopherol nicotinate compounds Inventor(s): Pearson; Don C. (Lakewood, WA), Richardson; Kenneth T. (Anchorage, AK) Assignee(s): Chronorx, LLC (Anchorage, AK) Patent Number: 6,423,847 Date filed: March 20, 2000 Abstract: A process of synthesis of D,.alpha.-tocopherol nicotinate compounds is presented. Therapeutic uses for this compound are described. The active agents are demonstrated to be complementary in their physiological functions especially as these relate to cellular and endothelial biochemistry and physiology and, ultimately to vascular health. The active components of the invention are selected for inclusion in a unique combination that clinically reduces risks of vasculopathy, DNA strand breakage and neuronal excitotoxicity in various diseases. In addition to the systemic vascular benefits acquired, improvement of the vascular health of the eye reduces the risk of glaucomatous optic nerve atrophy with its accompanying visual field loss and potential blindness and reduces conditions of risk for macular degeneration. Excerpt(s): The fields of the invention reside in biochemistry and in pharmacology. This invention relates to the synthesis and the therapeutic uses of various dosage forms comprised of D,.alpha.-tocopherol nicotinate and their uses as nutritional supplements and therapeutic agents. Dextro and levo stereoisomeric forms of a-tocopherol exist, but the dextro form is the most physiologically active and the most nutritionally useful. 1. Vascular oxidative stress brought about by superoxide radicals and oxidized lowdensity lipoproteins (oxLDL) are major factors contributing to decreased NO-dependent vasodilator functions in hypercholesterolemia and atherosclerosis. DAT antagonizes the oxLDL-related events in atherogenesis. DAT is generally regarded as the most important lipid-soluble, chain-breaking antioxidant in human plasma. Web site: http://www.delphion.com/details?pn=US06423847__

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Treatment of chronic hypertension and related conditions with thiol complexes Inventor(s): Pearson; Don C. (Lakewood, WA), Richardson; Kenneth T. (Anchorage, AK) Assignee(s): Chronorx, LLC (Anchorage, AK) Patent Number: 6,429,219 Date filed: May 3, 2000 Abstract: This invention relates to the synthesis of certain complexes of cysteine, Nacetylcysteine, N-(2-mercaptopropionyl)glycine, and L-2-oxothiazolidine-4-carboxylate and to the nutritional use of these and other related individual or complexed thiol-

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contributing glutathione predecessors. Clinical uses for these molecules and complexes in the beneficial modification of various physiological conditions and functions associated with aging, chronic glaucoma, diabetes mellitus, insulin resistance, macular degeneration, neurodegenerative diseases and vasoconstriction are described in particular. Excerpt(s): This invention is in the fields of pharmacology and biochemistry. It relates to the synthesis of certain complexes of L-cysteine, N-acetyl L-cysteine, N-(2-mercaptopropionyl)glycine, L-2-oxothiazolidine-4-carboxylate and the nutritional or clinical use of these and other related individual or complexed thiol contributing, glutathione predecessors. The use of these molecules and complexes in clinical presentations of chronic glaucoma, diabetes mellitus, macular degeneration, neurodegenerative diseases and vasoconstriction are described in particular. The eye is maintained in a homeostatic shape by a relatively stable intraocular pressure (IOP) that varies within a reasonably narrow range so long as the intraocular production of aqueous fluid remains equal to its exit from the eye. The optic nerve head can tolerate relatively high levels of IOP if the availability of oxygen from posterior ciliary arteries and optic nerve head arterioles remains adequate. However, if the global intraocular pressure is higher than the perfusion pressure driving oxygen through the arteriole into the surrounding tissues, decreasing amounts of oxygen will reach the optic nerve head and nerve disability will result. Web site: http://www.delphion.com/details?pn=US06429219__ •

Use of green porphyrins to treat neovasculature in the eye Inventor(s): Gragoudas; Evangelos S. (Lexington, MA), Miller; Joan W. (Winchester, MA) Assignee(s): Massachusetts Eye and Ear Infirmary (Boston, MA) Patent Number: 6,610,679 Date filed: April 2, 2001 Abstract: Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions. Excerpt(s): The invention is in the field of photodynamic therapy, specifically related to ocular conditions. More particularly, the invention concerns the use of green porphyrins in photodynamic therapeutic treatment of conditions characterized by unwanted neovasculature in the eye. Choroidal neovascularization leads to hemorrhage and fibrosis, with resultant visual loss in a number of eye diseases, including macular degeneration, ocular histoplasmosis syndrome, myopia, and inflammatory diseases. Age-related macular degeneration (AMD) is the leading cause of new blindness in the elderly, and choroidal neovascularization is responsible for 80% of the severe visual loss in patients with this diseases. Although the natural history of the disease is eventual quiescence and regression of the neovascularization process, this usually occurs at the cost of sub-retinal fibrosis and vision loss. Current treatment of AMD relies on occlusion of the blood vessels using laser photocoagulation. However, such treatment requires thermal destruction of the neovascular tissue, and is accompanied by full-thickness retinal damage, as well as damage to medium and-large choroidal vessels. Further, the subject is left with an atrophic scar and visual scotoma. Moreover, recurrences are common, and visual prognosis is poor.

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Web site: http://www.delphion.com/details?pn=US06610679__

Patent Applications on Macular Degeneration As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to macular degeneration: •

Amine salt of an integrin receptor antagonist Inventor(s): Humphrey, Guy R.; (Hillsborough, NJ), Xu, Wei; (North Wales, PA) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030004171 Date filed: June 18, 2002 Abstract: The tris(hydroxymethyl)aminomethane ("TRIS") salt of 3-(pyrimidin-5-yl)-9(5,6,7,8-tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoi- c acid is a potent antagonist of the integrin.alpha.v.beta.3 receptor and is useful for the prevention and/or treatment of osteoporosis and vascular restenosis, as well as conditions associated with excessive angiogenesis, such as macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth. The invention also relates to a process for the preparation of the novel salt as well as pharmaceutical compositions containing the salt and methods of using the salt. Excerpt(s): The present invention is related to U.S. provisional application Serial No. 60/299,344, filed Jun. 19, 2001, the contents of which are hereby incorporated by reference. The present invention relates to a novel amine salt of an integrin receptor antagonist. More particularly, the invention relates to the tris(hydroxymethyl)aminomethyl ("TRIS") salt of 3-(pyrimidin-5-yl)-9-(5,6- ,7,8tetrahydro-[1,8]-naphthyridin-2-yl)-nonanoic acid, which is a potent integrin.alpha.sub.v.beta.sub.3 receptor antagonist. The "TRIS" salt of the present invention is therefore useful for the treatment and prevention of diseases and conditions for which an antagonist of the integrin.alpha.sub.v.beta.sub.3 receptor is indicated. Integrin.alpha.sub.v.beta.sub.3 receptor antagonists have been described as being of use for the prevention and/or treatment of osteoporosis, vascular restenosis, macular degeneration, diabetic retinopathy, atherosclerosis, inflammatory arthritis, cancer, and metastatic tumor growth [see, for example, M. E. Duggan, et al., "Ligands to the integrin receptor.alpha.sub.v.beta.sub.3, Exp. Opin. Ther. Patents, 10: 1367-1383 (2000); M. Gowen, et al., "Emerging therapies for osteoporosis," Emerging Drugs, 5: 1-43 (2000); J. S. Kerr, et al., "Small molecule.alpha.sub.v integrin antagonists: novel anticancer agents," Exp. Opin. Invest. Drugs, 9: 1271-1291 (2000); and W. H. Miller, et al., "Identification and in vivo efficacy of small-molecule antagonists of integrin.alpha.sub.v.beta.sub.3 (the vitronectin receptor)," Drug Discovery Today, 5: 397-408 (2000)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

This has been a common practice outside the United States prior to December 2000.

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Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof Inventor(s): Sirois, Martin G.; (Quebec, CA) Correspondence: Marshall Gerstein & Borun; Sears Tower Suite 6300; 233 South Wacker Drive; Chicago; IL; 60606-6357; US Patent Application Number: 20030186920 Date filed: April 10, 2003 Abstract: The present invention provides antisense oligonucleotides that target the genes and mRNAs encoding mammalian VEGF receptors. Also provided are methods for designing and testing the antisense oligonucleotides. Such oligonucleotides can be used to reduce VEGF-induced inflammation and angiogenesis, for example, pathological angiogenesis, in mammals. Thus, the present invention also pertains to pharmaceutical compositions and formulations used in the treatment of mammals having a disease or disorder characterised by inflammation and/or pathological angiogenesis; including tumour growth and metastasis, ocular diseases (diabetic and perinatal hyperoxic retinopathies, age-related macular degeneration), arthritis, psoriasis and atherosclerosis. Excerpt(s): This application is a continuation in part of U.S. application Ser. No. 09/687,239, filed Oct. 13, 2000, which is hereby incorporated in its entirety. The present invention pertains to the field of antisense oligonucleotides for mammalian VEGF receptor genes and their use as anti-angiogenics and/or anti-inflammatory agents. Angiogenesis is a process by which new capillary vessels sprout from pre-existing ones, and can be summarised as the culmination of i) increased endothelial cell permeability to plasma proteins; ii) transmigration of inflammatory cells into extracellular matrix; iii) synthesis and release of degrading matrix molecules; iv) release of growth factors; v) migration and proliferation of endothelial cells to distant sites; and vi) capillary tube formation and vascular wall remodelling. Physiological angiogenesis is a highly coordinated process that exclusively occurs in healthy individuals under specific conditions, such as during wound healing, ovulation and pregnancy. At other times, the vasculature is extremely stable, with very low rates of new blood vessels (Fan et al., (1995) Trends Phaimacol. Sci. 16:57-66). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Apparatus and method for alleviation of symptoms by application of tinted light Inventor(s): Anderson, John Douglas; (Cambridge, GB), Jordan, Ian; (Ely, GB), Street, Graham Stewart Brandon; (Reading, GB), Thornton, Shane William; (Cambridge, GB) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030223036 Date filed: June 19, 2003 Abstract: Apparatus and a corresponding method for the diagnosis and alleviation of symptoms of visually induced physiological defects and/or pathological conditions is provided. A plurality of narrow-band light sources are combined to constitute a colour controllable lamp. A method for adjusting the settings of this lamp permits the optimum illumination for a particular subject to be found, whilst the latter carries out a task such

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as reading or writing. By use of the lamp to simulate the expected visual stimulus, to which the subject would be exposed if provided with viewing aids such as tinted spectacles and the like, an optimal selection from a database of such aids may be made or a new formulation defined. Inter alia, the symptoms of visual dyslexia, macular degeneration and visually induced migraine may be alleviated. Excerpt(s): The current invention is concerned with the provision or filtration of the illumination for a given task, such as reading or writing, and, specifically, with helping to alleviate the symptoms of certain physiological defects, such as dyslexia, or pathological conditions, such as migraine or macular degeneration, which may be suffered by the subject undertaking the task. It is known that the response of the visual system is affected by the stimuli, which it receives. The threshold for such stimulation varies between individuals and, under adverse conditions, can significantly reduce performance. When the visual system is over stimulated, it reacts in a number of ways. Amongst a variety of undesirable effects, which can be caused, two examples include a drop in convergence sufficiency and a reduction in the ability to accommodate or fuse images. In addition, visual dyslexia may become apparent and migraines can be caused. Visual dyslexia is a condition of impaired reading and writing ability due to visual perception or visualisation problems. It is apparent therefore that for some it is necessary to modify the visual stimulus by changing the spectral distribution in a specific task e.g. reading and writing in school. In summary, it is well established that the colour of ambient lighting has a major influence on the effects of disorders such as dyslexia, epilepsy and migraine. In the case of dyslexia some sufferers can alleviate their reading problems by covering the page with a transparent coloured overlay in order to block out those wavelengths of light which give rise to an aspect of their problem. These overlays typically remove various amounts of simple primary colours, such as red, green or blue light and whilst they may assist with reading, they are of no value for writing. In U.S. Pat. No. 5,855,428 (Wilkins) apparatus is described in which the spectral distribution of light from a fluorescent lamp to illuminate a surface to support reading material is altered by the interposition of specifically selected broadband filters. By adjustment of the position of the selected filter or filters different colours and saturation thereof can be selected. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Apparatus and methods for prevention of age-related macular degeneration and other eye diseases Inventor(s): Lin, J.T.; (Oviedo, FL) Correspondence: J.T. Lin; 4532 Old Carriage Trail; Oviedo; FL; 32765; US Patent Application Number: 20030105456 Date filed: December 4, 2001 Abstract: Surgical apparatus and surgical methods are proposed for the prevention of age-related macular degeneration (AMD) and choroidal neovascularization (CNV), and other eye diseases such as glaucoma by removal of the sclera tissue to reduce its rigidity and increase the flood flow and decrease pressure in the choriocapillaris. The disclosed preferred embodiments of the system consists of a tissue ablation means and a control means of ablation patterns and a fiber delivery unit. The basic laser beam includes UV lasers and infrared lasers having wavelength ranges of (0.15-0.36) microns and (0.5-3.2) microns and diode lasers of about 0.98, 1.5 and 1.9 microns. AMD and CNV are prevented, delayed or reversed by using an ablative laser to ablate the sclera tissue in a

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predetermined patterns outside the limbus to increase the elasticity of the sclera tissue surrounding the eye globe The surgery apparatus also includes non-laser device of radio frequency wave, electrode device, bipolar device and plasma assisted device Excerpt(s): The present invention relates to methods and apparatus for the prevention of age-related macular degeneration and other eye diseases. Age-related macular degeneration (AMD) is the leading cause of central visual loss in patients older than 50 years of age in the United States. The 10% of patients with wet degeneration accounts for 90% of the patients with severe vision loss to 20/200 or worse. The majority of eyes suffer severe visual loss of a result of Choroidal neovascularization (CNV), which is the formation of new blood vessels either between the retinal pigment epithelium and Bruch membrance or the subretinal space. CNV is a common manifestation of a variety of macular diseases and can result in severe vision loss. Typically, CNV complicates AMD, but it also can be seen in pathologic myopia, ocular histoplasmosis, angioid streaks, and ocular inflammatory diseases, and as an idiopathic condition. See Atlas of Ophthalmic Surgery, Chapt. 8, ed. by N. Jaffe, (Mosby-Wolfe, 1996). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Composition for the treatment and/or prevention of macular degeneration, method for its manufacture, and its use for treating the eye Inventor(s): Gazzotti, Paolo; (Geroldswil, CH), Richter, Christoph; (Zurich, CH), Shaban, Hamdy; (Dottikon, CH) Correspondence: Womble Carlyle Sandridge & Rice, Pllc; P.O. Box 7037; Atlanta; GA; 30357-0037; US Patent Application Number: 20030050283 Date filed: July 1, 2002 Abstract: Negatively charged phospholipids, as well as compositions including negatively charged phospholipids and possibly carotenoids and/or antioxidants, for treating the eye are disclosed. In a preferred embodiment, a composition comprising at least one negatively charged phospholipid except cardiolipin is used to treat age-related macular degeneration. Methods for producing the negatively charged phospholipids, as well as methods for producing the compositions including negatively charged phospholipids and possibly carotenoids and/or antioxidants for treating age-related macular degeneration, are also disclosed. Excerpt(s): The present invention relates to negatively charged phospholipids, as well as compositions including negatively charged phospholipids and possibly carotenoids and/or antioxidants, for treating the eye. In a preferred embodiment, the present invention relates to the use of negatively charged phospholipids for treating age-related macular degeneration. It also relates to methods for producing the negatively charged phospholipids, as well as methods for producing the compositions including negatively charged phospholipids and possibly carotenoids and/or antioxidants for treating agerelated macular degeneration. Age-related macular degeneration (AMD) affects 10 to 20% of the population over 65 years old and represents one of the main causes of serious vision damage and/or vision problems of older people in the industrial nations (Klein, R., Klein, B. E., and Linton, K. L. (1992) Ophthalmology 99, 933-943). One differentiates between the wet form of macular degeneration, which affects approximately 20% of the patients and is treatable using photodynamic therapy, and the dry form of AMD, which affects approximately 80% of the patients. The dry form of AMD typically has a slow

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course and has not been treatable until now. The molecular causes of this illness, which is particularly significant in geriatrics, have not been well researched. The newest investigations have shown that a pigment (A2E, N-retinyl-N-retinylidene ethanolamine), which forms naturally in the eye during the seeing process and increases tenfold with progressing age (Eldrid, G. E., Lasky, M. R. (1993) Nature 361, 724-726; Parish, C. A., Hashimoto, M., Nakanishi, K., Dylon, J., Sparrow, J. (1998) Proc. Natl. Acad. Sci. USA 95, 14609-14613), causes the death of pigment epithelial cells of the retina (Suter, M., Rem, C. E., Grimm, C., Wenzel, A., J{umlaut over (aa)}ttela, M., Esser, P., Kociok, N., Leist, M. and Richter, C. (2000) J. Biol. Chem. 275, 39625-39630). There are some indications that A2E is partially responsible for the dry form of AMD. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for inhibiting endothelial cell proliferation and regulating angiogenesis using cancer markers Inventor(s): Fortier, Anne H.; (Germantown, MD), Holaday, John W.; (Bethesda, MD) Correspondence: John S. Pratt, Esq; Kilpatrick Stockton, Llp; 1100 Peachtree Street; Suite 2800; Atlanta; GA; 30309; US Patent Application Number: 20030012792 Date filed: April 25, 2002 Abstract: Compositions and methods for regulating angiogenesis wherein the compositions comprise cancer markers are provided. Serine proteases and kallikreins exhibit potent antiangiogenic activity on human and other animal cells, particularly endothelial cells. More particularly, the use of a cancer marker, such as PSA, CEA, HCG, NSE, or CA19-9, to inhibit or ameliorate angiogenesis and angiogenesis-related diseases such as cancer, arthritis, macular degeneration, and diabetic retinopathy is disclosed. Excerpt(s): This application claims priority to U.S. patent application Ser. No. 09/413,049, filed Oct. 6, 1999, which claims priority to U.S. application Ser. No. 09/316,802, filed May 21, 1999, which claims priority to U.S. Provisional Application Serial No. 60/086,586, filed May 22, 1998, each of which is incorporated herein by reference in its entirety. This invention relates to a novel use of cancer markers for preventing, ameliorating or treating a cell proliferative disease or disorder. The invention further relates to novel compositions and methods for treating angiogenesisrelated diseases such as angiogenesis-dependent cancer. Cancer markers are not cancerspecific but rather cancer-associated substances that can be elevated in sera from healthy individuals under various conditions and from patients with benign tumors. The discovery of cancer markers has significantly enhanced not only diagnosis of cancer but has also contributed to the monitoring of cancer patients for assessing disease progression. A rise in cancer markers is a yardstick with which benign diseases can be distinguished from metastatic disease and can also be used to evaluate the efficacy of treatments. A decline in cancer markers is often a predictor of possible residual disease if the timing of blood sampling is soon after therapy. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Compositions and methods for prevention and treatment of chronic diseases and disorders including the complications of diabetes mellitus Inventor(s): Kosbab, John V.; (Dillon, CO) Correspondence: Greenlee, Winner And Sullivan, P.C.; Suite 201; 5370 Manhattan Circle; Boulder; CO; 80303; US Patent Application Number: 20030108624 Date filed: June 28, 2002 Abstract: This invention relates to nutrient and therapeutic compositions for treatment and prevention of symptoms and disease conditions associated with microangiopathy and macroangiopathy and to methods using the compositions. In particular, the invention relates to compositions useful in the treatment of diabetic retinopathy and nephropathy, to compositions useful in the treatment of other retinal disorders including macular degeneration and cataracts, to compositions useful in wound healing, to compositions useful for treatment and prevention of neuropathy, to compositions useful for treatment and prevention of cardiovascular disease and to compositions useful for the treatment and prevention of dental and periodontal disorders. Excerpt(s): The application is a continuation of U.S. patent application Ser. No. 09/827,251, filed Apr. 5, 2001, which is a continuation of U.S. patent application Ser. No. 09/018,273, filed Feb. 4, 1998, which claims priority to U.S. Provisional Application Serial No. 60/037,084, filed Feb. 4, 1997, and No. 60/043,262, filed Apr. 17, 1997, all of which are incorporated by reference in their entirety herein to the extent not inconsistent with the disclosure herein. This invention relates to the use of nutrient and therapeutic compositions to ameliorate the disease symptoms and conditions associated with vascular and capillary disorders: microangiopathy and macroangiopathy. Compositions of this invention include antioxidants, neovascular regulators, promoters or cofactors involved in collagen synthesis, as well as vitamins and minerals to supplement deficiencies. Vascular degeneration, both macroangiopathy and microangiopathy (capillary degeneration), is believed to be the root cause of a variety of degenerative disease conditions that affect a substantial portion of the population. Vascular degeneration is directly associated with cardiovascular disease, atherosclerosis and plaque deposition and indirectly associated with degenerative conditions of the retina (including retinopathy), kidney (nephropathy) and nervous system (neuropathy), as well as skin ulcers. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Diagnostics and therapeutics for arterial wall disruptive disorders Inventor(s): Hageman, Gregory S.; (Coralville, IA) Correspondence: Townsend And Townsend And Crew Llp; Two Embarcadero Center, 8th Floor; San Francisco; CA; 94111-2422; US Patent Application Number: 20030149997 Date filed: February 22, 2000 Abstract: The invention provides diagnostics, therapeutics and drug screening assays for arterial wall disruptive disorders, based on the discovery of a high level of correlation between the incidence of arterial wall disruptive disorders and the incidence

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of Age Related Macular Degeneration (AMD). In one embodiment, the arterial wall disruptive disorder is an aortic aneurysm. Excerpt(s): The invention relates to diagnostics, therapeutics and animal models for arterial wall disruptive disorders, including arterial aneurysmal disease. Disorders of the peripheral arterial system cause their pathological effects by two general mechanisms: obstruction of the arterial lumen or disruption of the vessel wall. Arterial obstruction most commonly results from atherosclerosis, although other causes of luminal blockage may be identified, including inflammatory conditions, external compression, emboli, thrombi or fibromuscular dysplasia. Arterial obstructive disorders typically affect multiple sites within the arterial tree. Disruption of the arterial wall results in aneurysm formation, arterial wall dissection or frank arterial rupture. Arterial aneurysm formation is most commonly related to atherosclerosis. Aneurysms may also result from infections, cystic medial necrosis, congenital anomalies or trauma. As used herein, trauma shall include both non-iatrogenic and iatrogenic processes. Arterial wall dissection may arise as a complication of an aneurysm or as an independent event. Arterial wall dissection in the absence of a pre-existing aneurysm may occur spontaneously, or it may result from trauma. Frank arterial rupture may result from the progressive expansion of an arterial aneurysm beyond a certain critical diameter. If no aneurysm is present, the most common cause of arterial rupture is some type of arterial trauma. Artery wall disruption may affect multiple sites, or may be localized to only one location. Aneuysmal disorders or aneurysmal diseases, as these terms are used herein, include those processes that result in aneurysm formation in a segment of at least one artery. An aneurysm is understood to be a permanent localized dilatation of an artery with increase in diameter of 1.5 times normal, recognizing that values for normal arterial diameter vary with age, sex and blood pressure. (Vermilion B D et al., "A review of one hundred forty-seven popliteal aneurysms with long-term follow-up," Surgery 90:1009, 1981). Aneurysms cause symptoms by rupturing, by compressing adjacent structures, by leaking, by obstructing flow to vessels that arise from the segment of artery affected by the aneurysm, and by accumulating thrombus within the vessel lumen at the site of the aneurysm, said thrombus being capable of suddenly occluding the vessel or of sending smaller emboli into the distal arterial tree. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Differentially-expressed genes and polypeptides in angiogenesis Inventor(s): Jay, Gilbert; (North Bethesda, MD), Sun, Zairen; (Rockville, MD) Correspondence: Origene Technologies, Incorporated; 6 Taft Court; Suite 100; Rockville; MD; 20850; US Patent Application Number: 20030148334 Date filed: October 11, 2002 Abstract: The present invention relates to all facets of polynucleotides, the polypeptides they encode, antibodies and specific binding partners thereto, and their applications to research, diagnosis, drug discovery, therapy, clinical medicine, forensic science and medicine, etc. The polynucleotides are expressed during angiogenesis and are therefore useful in variety of ways, including, but not limited to, as molecular markers, as drug targets, and for detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, determining predisposition to, etc., diseases and conditions, such as abnormal, insufficient, excessive, etc., angiogenesis, such as inflammatory diseases, such as rheumatoid arthritis, osteoarthritis, asthma, pulmonary fibrosis, age-related macular

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degeneration (ARMD), diabetic retinopathy, macular degeneration, and retinopathy of prematurity (ROP), endometriosis, cancer, Coats' disease, peripheral retinal neovascularization, neovascular glaucoma, psoriasis, retrolental fibroplasias, angiofibroma, inflammation, etc Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/328,395, filed Oct. 12, 2002, which is hereby incorporated by reference in its entirety. Angiogenesis, the process of blood vessel formation, is a key event in many physiological processes that underlie normal and diseased tissue function. During ontogeny, angiogenesis is necessary to establish to the network of blood vessels required for normal cell, tissue and organ development and maintenance. In the adult organism, the production of new blood vessels is needed for organ homeostasis, e.g., in the cycling of the female endometrium, for blood vessel maturation during wound healing, and other processes involved in the maintenance of organism integrity. It also is important in regenerative medicine, including, e.g., in promoting tissue repair, tissue engineering, and the growth of new tissues, inside and outside the body. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Endothelial-cell binding peptides for diagnosis and therapy Inventor(s): Gyuris, Jeno; (Winchester, MA), Lamphere, Lou; (Newton, MA), Morris, Aaron J.; (Brighton, MA), Tsaioun, Katherine; (Belmont, MA) Correspondence: Ropes & Gray; One International Place; Boston; MA; 02110-2624; US Patent Application Number: 20030166004 Date filed: November 1, 2002 Abstract: The present invention relates to peptides and their derivatives which bind to endothelial cells and inhibit their proliferation in in vitro assays, e.g., also referred to herein as endothelial cell binding peptide (ECBP) or ECBP sequence. These compositions may be combined with a pharmaceutically acceptable excipient or carrier and used to inhibit angiogenesis and angiogenesis-related diseases such as cancer, arthritis, macular degeneration, and diabetic retinopathy. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/334,822, filed on Nov. 1, 2001, the entire contents of which are incorporated herein by reference. Angiogenesis, the process by which new blood vessels are formed, is essential for normal body activities including reproduction, development and wound repair. Although the process is not completely understood, it is believed to involve a complex interplay of molecules which regulate the growth of endothelial cells (the primary cells of capillary blood vessels). Under normal conditions, these molecules appear to maintain the microvasculature in a quiescent state (i.e. one of no capillary growth) for prolonged periods which may last for as long as weeks or, in some cases, decades. When necessary (such as during wound repair), these same cells can undergo rapid proliferation and turnover within a 5 day period (Folkman, J. and Shing, Y., The Journal of Biological Chemistry, 267(16), 10931-10934, and Folkman, J. and Klagsbrun, M., Science, 235, 442-447 (1987). Although angiogenesis is a highly regulated process under normal conditions, many diseases (characterized as angiogenic diseases) are driven by persistent unregulated angiogenesis. Otherwise stated, unregulated angiogenesis may either cause a particular disease directly or exacerbate an existing pathological condition. For example, ocular neovascularization has been implicated as the most common cause of blindness and dominates approximately 20 eye diseases. In certain

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existing conditions, such as arthritis, newly formed capillary blood vessels invade the joints and destroy cartilage. In diabetes, new capillaries formed in the retina invade the vitreous, bleed, and cause blindness. Growth and metastasis of solid tumors are also dependent on angiogenesis (Folkman, J., Cancer Research, 46, 467-473 (1986), Folkman, J., Journal of the National Cancer Institute, 82, 4-6 (1989). It has been shown, for example, that tumors which enlarge to greater than 2 mm must obtain their own blood supply and do so by inducing the growth of new capillary blood vessels. Once these new blood vessels become embedded in the tumor, they provide a means for tumor cells to enter the circulation and metastasize to distant sites such as liver, lung or bone (Weidner, N., et al., The New England Journal of Medicine, 324(1), 1-8 (1991). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Eyeglass manufacturing method using variable index layer Inventor(s): Dreher, Andreas W.; (Escondido, CA) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030081172 Date filed: October 25, 2001 Abstract: An Eyeglass Manufacturing Method Using Epoxy Aberrator includes two lenses with a variable index material, such as epoxy, sandwiched in between. The epoxy is then cured to different indexes of refraction that provide precise corrections for the patient's wavefront aberrations. The present invention further provides a method to produce an eyeglass that corrects higher order aberrations, such as those that occur when retinal tissue is damaged due to glaucoma or macular degeneration. The manufacturing method allows for many different applications including, but not limited to, supervision and transition lenses. Excerpt(s): The present invention relates generally to an eyeglass manufacturing method using a layer with a variable index of refraction. More specifically, the present invention pertains to patient-specific spectacle lenses manufactured with an variable index aberrator in order to more accurately correct lower order aberrations and additionally correct higher order aberrations. The present invention also provides a means for correcting vision problems caused by retinal dysfunction. Present manufacturing techniques for eyeglass lenses are capable of producing lenses that correct only the lower order (sphere and cylinder) aberrations. Customarily, lens blanks are available in discrete steps of refractive power of 0.25 diopters. In most cases, these steps are too large to create optimum vision for a patient's eye. Current manufacturing techniques do not effectively treat vision problems resulting from retinal dysfunction. For example, in macular degeneration, patients suffer from vision loss in selective areas of the fundus, typically close to the center of vision. Laser treatment of the affected areas further destroys retinal tissue, causing blindness at the treated areas. Clinical studies have shown that the human eye and brain are capable of switching to other areas of the retina to substitute the damaged area with an undamaged area. In other words, damaged areas in the retina are essentially bypassed by the brain. Ultimately, vision loss will occur as a portion of an image falls on the damaged retina. Consequently, there is a need to manufacture an eyepiece such that the image may be "warped" around the dysfunctional tissue in order to allow the entire image to focus on the remaining healthy tissue.

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Guide means for intraocular injection Inventor(s): Billson, Francis Alfred; (Sydney, AU), Gillies, Mark Cedric; (Randwick, AU), Penfold, Philip Leslie; (Sydney, AU) Correspondence: Ladas & Parry; 26 West 61st Street; New York; NY; 10023; US Patent Application Number: 20030060763 Date filed: September 12, 2002 Abstract: This invention relates to the art of intraocular injection as a means of treating various conditions of the eye. In particular it relates to a plaque containing guide means for location of a needle entry point into the eye which thereby facilitates such injection. The invention also relates to a kit which includes (1) an intraocular composition containing an active compound able to treat the particular condition; (2) a syringe for dispensing the composition through a needle coupled to the syringe, the syringe having dimensions such that blockage of the needle is minimised; and (3) a plaque containing guide means for location of the needle entry points into the eye. In one form, it provides for a kit which includes (i) an anti-inflammatory steroid which is the active agent in treating the macular degeneration; (ii) a syringe need for the delivery of that steroid through a needle coupled to the syringe, and (iii) a plaque which facilitates correct positioning of the needle. Excerpt(s): In one form, it provides for a kit which includes (i) an anti-inflammatory steroid which is the active agent in treating the macular degeneration; (ii) a syringe used for the delivery of that steroid through a needle coupled to the syringe, and (iii) a plaque which facilitates correct positioning of the needle. Intraocular injection is known. For example, it is known to inject antibodies to treat intraocular infection. However, various problems may arise when using this technique. For example, if a constituent of the composition is present as sufficiently large particles, it may settle out in the vial before being drawn up into the syringe, thereby providing a non-uniform concentration of that constituent compared to its concentration in the vial. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hydroxamic and carboxylic acid derivatives Inventor(s): Baxter, Andrew Douglas; (Cambridge, GB), Dyke, Hazel Joan; (Cambridge, GB), Hannah, Duncan Robert; (Cambridge, GB), Keily, John Fraser; (Cambridge, GB), Watson, Robert John; (Cambridge, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030092727 Date filed: October 25, 2002 Abstract: Pharmacologically active compounds are provided as well as pharmaceutical compositions and methods for treating cancer; inflammation; an autoimmune, infectious or ocular disease; or age-related macular degeneration in a mammal. Excerpt(s): This invention relates to hydroxamic and carboxylic acid derivatives, and to their use in medicine. Metalloproteinases, including matrix metalloproteinase (I),

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collagenase, gelatinase and TNF.alpha. convertase (TACE), and their modes of action, and also inhibitors thereof and their clinical effects, are described in WO-A-96/11209, WO-A-97/12902 and WO-A-97/19075, the contents of which are incorporated herein by reference. MMP inhibitors may also be useful in the inhibition of other mammalian metalloproteinases such as the ADAM or ADAM-TS families. Compounds which have the property of inhibiting the action of metalloproteinases involved in connective tissue breakdown, such as collagenase, stromelysin and gelatinase, have been shown to inhibit the release of TNF.alpha. both in vitro and in vivo See Gearing et al (1994), Nature 370:555-557; McGeehan et al (1994), Nature 370:558-561; GB-A-2268934, and WO-A93/20047. All of these reported inhibitors contain a hydroxamic acid zinc-binding group, as do the imidazole-substituted compounds disclosed in WO-A-95/23790. Other compounds that inhibit MB and/or TNF.alpha. are described in WO-A-95/13289, WOA-96/11209, WO-A-96/035687, WO-A-96/035711, WO-A-96/035712 and WO-A96/035714. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Increasing growth factor production by cells Inventor(s): Chaum, Edward; (Germantown, TN) Correspondence: Margaret J. Mclaren, PH.D., ESQ.; Akerman Senterfitt; Suite 400; 222 Lakeview Avenue; West Palm Beach; FL; 33402-3188; US Patent Application Number: 20030186918 Date filed: March 26, 2003 Abstract: Disclosed are methods and compositions for growth factor gene therapy for conditions involving degeneration or injury of cells of the retina, including age-related macular degeneration. Included in the invention are non-viral vectors for delivery of growth factor fusion proteins, cells transduced with such vectors, and methods of treatment using these vectors. Excerpt(s): This application claims priority from U.S. Provisional Application Serial No. 60/367,873 filed Mar. 27, 2002. The foregoing is incorporated herein by reference. This invention relates generally to the fields of molecular biology and medicine. More particularly, the invention relates to methods of gene therapy for eye diseases using growth factors. The retinal pigment epithelium (RPE) serves many critical functions in maintaining the health of the neurosensory retina. One of these functions is the production of growth factors (also known as cytokines, neurotrophic factors, and trophic hormones), that have both paracrine and autocrine activity in the RPE (Waldbillig R J, et al. J Neurochem 1991, 57:1522-1533; Takagi H, et al., Invest Ophthalmol Vis Sci 1994, 35:916-923; Schweigerer I, et al., Biochem Biophys Res Commun 1987, 143:934-940; Martin D M et al., Brain Res Mol Brain Res 1992, 12:181186). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Indocyanine green (ICG) compositions and related methods of use Inventor(s): Alam, Abu; (Lake Forest, IL), Chavan, Ashok J.; (Bloomington, IL), Flower, Robert W.; (Hunt Valley, MD) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20030060718 Date filed: December 27, 2001 Abstract: Aqueous indocyanine green (ICG) composition exhibiting enhanced stability, as well as enhanced ICG concentration, as compared to presently available ICG products. The composition comprises an aqueous ICG composition comprising ICG at a concentration of at least about 10 mg/ml and an aqueous diluent, wherein the composition is stable for at least 24 hours. Diagnostic and therapeutic methods for using these aqueous compositions are also contemplated, e.g., angiography, dye-enhanced photocoagulation, photodynamic therapy, for a variety of conditions, including AgeRelated Macular Degeneration (ARMD), lesions and tumors. Excerpt(s): This application is a continuation-in-part of co-pending U.S. patent application Ser. No. 09/393,456, filed Sep. 10, 1999, which is incorporated by reference. The present invention generally concerns indocyanine green compositions useful in the diagnosis of organ function and disease in animals, e.g., humans. Indocyanine green (ICG) is a well-known fluorsecent dye. The dye is presently marketed by Akorn, Inc. (Buffalo Grove, Ill.) under the trademark IC GREEN.TM. ICG is presently supplied as a lyophilized powder (25 mg) for reconstitution with 5 ml sterile water for injection (WFI). The reconstituted ICG composition (at 5 mg/ml) should be used within 10 hours, with any unused portion being discarded. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Macular degeneration diagnostics and therapeutics Inventor(s): Sheffield, Val C.; (Coralville, IA), Stone, Edwin M.; (Iowa City, IA) Correspondence: Needle & Rosenberg P C; 127 Peachtree Street N E; Atlanta; GA; 303031811; US Patent Application Number: 20030138798 Date filed: July 8, 2002 Abstract: Therapeutics and diagnostics based on the identification of genetic mutations, which cause Macular Degeneration (MD) is disclosed. Excerpt(s): Macular degeneration is a clinical term that is used to describe a variety of diseases that are all characterized by a progressive loss of central vision associated with abnormalities of Bruch's membrane and the retinal pigment epithelium. These disorders include very common conditions that affect older patients (age related macular degeneration or AMD) as well as rarer, earlier-onset dystrophies that in some cases can be detected in the first decade of life.sup.1-18. The genes associated with some of these dystrophies have been mapped,.sup.5-14 and in three cases, blue-cone monochromasy,.sup.15 pattern dystrophy,.sup.16-17 and Sorsby fundus dystrophy,.sup.18 actually identified. However, none of the latter genes has been found to be responsible for a significant fraction of typical late-onset macular degeneration. In developed countries, AMD is the most common cause of legal blindness in older

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patients.sup.19 The hallmark of this condition is the presence of drusen, which are ophthalmoscopically visible, yellow-white hyaline excrescences of Bruch's membrane. In some families, drusen are heritable in an autosomal dominant fashion. Currently, there is no therapy that is capable of significantly slowing the degenerative progression of AMD, and treatment is limited to laser photocoagulation of the subretinal neovascular membranes that occur in 10-15% of affected patients. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Materials and methods for treating ocular-related disorders Inventor(s): Brough, Douglas E.; (Gaithersburg, MD), Kovesdi, Imre; (Rockville, MD), McVey, Duncan L.; (Derwood, MD), Wei, Lisa; (Gaithersburg, MD) Correspondence: Leydig Voit & Mayer, Ltd; Two Prudential Plaza, Suite 4900; 180 North Stetson Avenue; Chicago; IL; 60601-6780; US Patent Application Number: 20030045498 Date filed: August 2, 2002 Abstract: The present invention is directed to a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder, e.g., ocular neovascularization or age-related macular degeneration. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and the same or different nucleic acid sequence encoding a neurotrophic agent. The method also can comprise contacting an ocular cell with different expression vectors, each comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a nucleic acid sequence encoding a neurotrophic agent. In addition, the present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof. Excerpt(s): This patent application is a continuation of International Patent Application No. PCTIUS01/04203, filed Feb. 9, 2001, which designates the U.S., and which claims the benefit of U.S. Provisional Patent Application No. 60/228,337, filed Aug. 28, 2000, and which also claims the benefit of U.S. Provisional Patent Application No. 60/181,743, filed Feb. 11, 2000, and which also is a continuation-in-part of U.S. patent application Ser. No. 09/599,997, filed Jun. 23, 2000, which claims the benefit of U.S. Provisional Patent Application No. 60/181,743, filed Feb. 11, 2000. The present invention relates to a method of prophylactically or therapeutically treating an ocular disorder as well as materials useful for treating an ocular disorder. An overwhelming majority of the world's population will experience some degree of vision loss in their lifetime. Vision loss affects virtually all people regardless of age, race, economic or social status, or geographical location. Ocular-related disorders, while often not life threatening, necessitate life-style changes that jeopardize the independence of the afflicted individual. Vision impairment can result from most all ocular disorders, including diabetic retinopathies, proliferative retinopathies, retinal detachment, toxic retinopathies, retinal vascular diseases, retinal degenerations, vascular anomalies, agerelated macular degeneration and other acquired disorders, infectious diseases, inflammatory diseases, ocular ischemia, pregnancy-related disorders, retinal tumors, choroidal tumors, choroidal disorders, vitreous disorders, trauma, cataract complications, dry eye, and inflammatory optic neuropathies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for treating visual impairment through the prophylactic administration of a Morinda citrifolia-based naturaceutical Inventor(s): Ocampo, Enrique; (El Paso, TX), Jensen, Claude Jarakae; (Cedar Hills, UT) Correspondence: Kirton & Mcconkie; 1800 Eagle Gate Tower; 60 East South Temple; Salt Lake City; UT; 84111; US Patent Application Number: 20030134002 Date filed: November 1, 2002 Abstract: Implementation of the present invention takes place in association with the utilization of one or more processed products produced from the Indian Mulberry plant, scientifically known as Morinda citrifolia L., to treat one or more eye disorders that affect vision, such as glaucoma, diabetic retinopathy, retinitis pigmentosa, cataracts, agerelated macular degeneration, night blindness, color blindness, and other related conditions. The processed Morinda citrifolia products from the Indian Mulberry plant may be in the form of a dietary supplement, eye drops, or in another suitable form. Excerpt(s): The present invention relates to methods and naturaceutical formulations and substances for treating and preventing ocular or visual impairments. Specifically, the present invention relates to Morinda citrifolia-based methods and naturaceutical formulations and substances for treating pre-existing ocular impairments, as well as to Morinda citrifolia-based methods and naturaceutical formulations and substances for preventing the onset or reducing the onset potential of future or additional ocular impairments. The present invention is particularly suited for treatment and prevention of ocular impairments as commonly experienced in mammals, and particularly humans. The eye is an organ that collects light and turns it into electronic messages that are sent to the brain. The brain then turns those signals into a picture for an individual to see. Since individuals have two eyes, two pictures are usually created, which accounts for depth of vision. Most of depth of vision occurs from judging the relative size of the objects seen. The eye includes several intricate parts or components. The eyelids hold the lashes, keep the eye moist, and shield it from intense light. The conjunctiva is a membrane that covers most of the eyeball and allows the lids to gently glide over the eye. The clear cornea covers the iris, and works like a watch-face for the eye. It allows a small amount of light to enter the eye through the pupil. Then, along with the natural lens, it acts like a camera-lens and focuses the image onto the retina. The retina is like the film in a "ocular" camera. It lines the inside of the eye, and is mostly clear. The retina has very few blood vessels that would disturb the retinal picture. Since the retina has so few blood vessels and does a lot of work, it needs to be nourished by a blood vessel layer beneath it. This sub-layer blood vessel is called the choroid or uvea. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of treating angiogenesis-related disorders Inventor(s): Bingaman, David P.; (Fort Worth, TX), Gamache, Daniel A.; (Arlington, TX), Graff, Gustav; (Cleburne, TX), Kapin, Michael A.; (Arlington, TX), Yanni, John M.; (Burleson, TX) Correspondence: Alcon Research, LTD.; R&d Counsel, Q-148; 6201 South Freeway; Fort Worth; TX; 76134-2099; US Patent Application Number: 20030187072 Date filed: February 14, 2003

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Abstract: The use of 3-benzolphenylacetic acids and derivatives, including nepafenac, to treat angiogenesis-related disorders, including ophthalmic angiogenesis-related disorders such as diabetic retinopathy and exudative macular degeneration, is disclosed. Excerpt(s): 3-benzolphenylacetic acid and certain of its derivatives are known to possess anti-inflammatory activity. U.S. Pat. Nos. 4,254,146, 4,045,576, 4,126,635, and 4,503,073, and U.K. Patent Application Nos. 2,071,086A and 2,093,027A disclose various 3benzolphenylacetic acids, salts and esters, and hydrates thereof, having antiinflammatory activity. U.S. Pat. No. 4,568,695 discloses 2-amino-3-benzoylphenylethyl alcohols having anti-inflammatory activity. U.S. Pat. No. 4,313,949 discloses 2-amino-3benzoyl-phenylacetamides having anti-inflammatory activity. This invention relates to the use of certain 3-benzolphenylacetic acids and derivatives to treat or prevent angiogenic diseases. Certain derivatives of 2-amino-3-benzoylbenzeneacetic acid (amfenac) and 2-amino-3-(4-chloro-benzoyl)benzeneacetic acid have also been evaluated by Walsh et al., J. Med Chem., 33:2296-2304 (1990), in an attempt to discover nonsteroidal anti-inflammatory prodrugs with minimal or no gastrointestinal side effects upon oral administration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method to treat age-related macular degeneration Inventor(s): Peyman, Gholam A.; (New Orleans, LA) Correspondence: Wood, Herron & Evans, Llp; 2700 Carew Tower; 441 Vine Street; Cincinnati; OH; 45202; US Patent Application Number: 20030093064 Date filed: November 13, 2001 Abstract: Age-related macular degeneration (AMD) results in the formation of new blood vessels in the eye. The walls of these vessels leak fluid, which causes scarring in the surrounding tissue, resulting in reduced vision or loss of vision. Photodynamic therapy (PDT) alone has been used to treat AMD, but many retreatments are needed, which cause further damage to the already diseased area. Laser treatment to coagulate the fluid actually causes additional new vessels to form. However, the inventive method of treating patients with both PDT and laser coagulation surprisingly either improved vision, or prevented further loss of vision. Moreover, the combined treatment eliminated the need for retreatment, and did not generate new vessel growth. Laser coagulation and PDT may be administered within the same treatment session or either may be administered first and the other may be administered within ninety days. Excerpt(s): The invention is directed generally to an ophthalmological process, and more specifically to a process to improve, maintain, or reduce loss of visual acuity in a patient having or at risk for developing macular degeneration. In the mammalian eye, macular degeneration (also called age related macular degeneration, AMD) is a pathological condition that is the most common cause of legal blindness among individuals over the age of 60, with an incidence ranging from 11% to 18.5% in individuals over the age of 85. In the United States, AMD affects roughly 3.6 million individuals, with over 200,000 new cases developing annually. One type of AMD results in proliferation of new blood vessels in the subretinal area, typically the choroid. In the normal retina, both the large blood vessels and the capillaries have intact vessel walls. In the normal choroid, the large vessels have intact vessel walls, but the capillaries have fenestrations or openings

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in their walls. In patients with AMD, new blood vessels proliferate from the choriocapillaries through defects in Bruch's membrane beneath or on top of retinal pigment epithelium (RPE), and form vascular membranes. The resulting choroidal neovascularizations (new vessels in the choroid) occur in about 8-10% of all patients with AMD, and are also seen in patients with pathologic myopia and presumed ocular histoplasmosis syndrome, as well as other idiopathic conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods and compositions for treating conditions of the eye Inventor(s): Gragoudas, Evangelos S.; (Lexington, MA), Miller, Joan W.; (Winchester, MA), Renno, Reem Z.; (Boston, MA) Correspondence: Testa, Hurwitz & Thibeault, Llp; High Street Tower; 125 High Street; Boston; MA; 02110; US Patent Application Number: 20030175282 Date filed: May 5, 2003 Abstract: Provided are methods and compositions for the photodynamic therapy (PDT) of ocular conditions characterized by the presence of unwanted choroidal neovasculature, for example, neovascular age-related macular degeneration. The selectivity and sensitivity of the PDT method can be enhanced by combining the PDT with an anti-angiogenesis factor, for example, angiostatin or endostatin, or with an apoptosis-modulating factor. Furthermore, the selectivity and sensitivity of the PDT may be further enhanced by coupling a targeting moiety to the photosensitizer so as to target the photosensitizer to choroidal neovasculature. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/181,641, filed Feb. 10, 2000, the disclosure of which is incorporated herein by reference. The invention relates generally to photodynamic therapy-based methods and compositions for treating ocular conditions and, more specifically, the invention relates to photodynamic therapy-based methods and compositions for treating ocular conditions characterized by unwanted choroidal neovasculature. Choroidal neovascularization can lead to hemorrhage and fibrosis, with resulting visual loss in a number of conditions of the eye, including, for example, age-related macular degeneration, ocular histoplasmosis syndrome, pathologic myopia, angioid streaks, idiopathic disorders, choroiditis, choroidal rupture, overlying choroid nevi, and certain inflammatory diseases. One of the disorders, namely, age-related macular degeneration (AMD), is the leading cause of severe vision loss in people aged 65 and above (Bressler et al. (1988) SURV. OPHTHALMOL. 32, 375-413, Guyer et al. (1986) ARCH. OPHTHALMOL. 104, 702-705, Hyman et al. (1983) AM. J. EPIDEMIOL. 188, 816-824, Klein & Klein (1982) ARCH. OPHTHALMOL. 100, 571-573, Leibowitz et al. (1980) SURV. OPHTHALMOL. 24, 335-610). Although clinicopathologic descriptions have been made, little is understood about the etiology and pathogenesis of the disease. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compositions for treatment of ocular neovascularization and neural injury Inventor(s): DeVries, Gerald W.; (Laguna Hills, CA), Wheeler, Larry A.; (Irvine, CA) Correspondence: Carlos A. Fisher; Allergan, INC.; T2-7h; 2525 Dupont Drive; Irvine; CA; 92612; US Patent Application Number: 20030082183 Date filed: April 26, 2002 Abstract: Methods and compositions for the treatment of ocular neovascularization and macular degeneration. The invention includes combining photodynamic therapy with administration of a neuroprotectant and a neovascularization inhibitor. Excerpt(s): Loss of visual acuity is a common problem associated with aging and with various conditions of the eye. Particularly troublesome is the development of unwanted neovascularization in the cornea, retina or choroid. Choroidal neovascularization leads to hemorrhage and fibrosis, with resultant visual loss in a number of recognized eye diseases, including macular degeneration, ocular histoplasmosis syndrome, myopia, diabetic retinopathy and inflammatory diseases. Age-related macular degeneration (AMD) is the leading cause of new blindness in the elderly, and choroidal neovascularization is responsible for 80% of the severe visual loss in patients with this disease. Although the natural history of the disease is eventual quiescence and regression of the neovascularization process, this usually occurs at the cost of sub-retinal fibrosis and vision loss. Traditional treatment of AMD relies on occlusion of the blood vessels using laser photocoagulation. However, such treatment requires thermal destruction of the neovascular tissue, and is accompanied by full-thickness retinal damage, as well as damage to medium and large choroidal vessels. Further, the subject is left with an atrophic scar and visual scotoma. Moreover, recurrences are common, and visual prognosis is poor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods of screening and using inhibitors of angiogenesis Inventor(s): Baciu, Peter C.; (Laguna Niguel, CA), Manuel, Virna M.; (Lawndale, CA), Zhang, Heying; (Rockville, MD) Correspondence: Carlos A. Fisher; Allergan, INC.; T2-7h; 2525 Dupont Drive; Irvine; CA; 92623; US Patent Application Number: 20030171271 Date filed: April 3, 2002 Abstract: A method of screening for agents which are able to inhibit angiogenesis. Such agent have therapeutic application in the treatment of conditions including cancer, macular degeneration and retinopathies. Also included are methods of treating a patient having a pathological condition characterized by an increase in angiogenesis which comprises administering to the patient an agent capable of inhibiting activation of an integrin subunit. Excerpt(s): This patent application claims benefit of priority under 35 USC.sctn. 119(e) to provisional patent application No. 60/281,512, filed Apr. 4, 2001, which is hereby incorporated by reference herein. Angiogenesis is the method by which new blood vessels form from existing vasculature in an animal. The process is distinct from

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vasculogenesis, in that the new endothelial cells lining the vessel arise from proliferation of existing cells, rather than differentiating from stem cells. The process is invasive and dependent upon proteolyisis of the extracellular matrix (ECM), migration of new endothelial cells, and synthesis of new matrix components. Angiogenesis occurs during embryogenic development of the circulatory system; however, in adult humans, angiogenesis only occurs as a response to a pathological condition (except during the reproductive cycle in women). Thus, in adults, angiogenesis is associated with conditions including wound healing, arthritis, tumor growth and metastasis, as well as in ocular conditions such as retinopathies, macular degeneration and corneal ulceration and trauma. In each case the progression of angiogenesis is similar: a stimulus results in the formation of a migrating column of endothelial cells. Proteolytic activity is focused at the advancing tip of this "vascular sprout", which breaks down the ECM sufficiently to permit the column of cells to infiltrate and migrate. Behind the advancing front, the endothelial cells differentiate and begin to adhere to each other, thus forming a new basement membrane. The cells then cease proliferation and finally define a lumen for the new arteriole or capillary. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods of treating ophthalmic disorders with epoxy-steroidal aldosterone receptor antagonists Inventor(s): Aiken, James W.; (Basking Ridge, NJ) Correspondence: Senniger Powers Leavitt And Roedel; One Metropolitan Square; 16th Floor; ST Louis; MO; 63102; US Patent Application Number: 20030158162 Date filed: December 12, 2002 Abstract: A method for treating or preventing ophthalmic disorders comprising the administration of one or more aldosterone receptor antagonists that contain a 9,11epoxy moiety, such as eplerenone is disclosed. The method results in a reduction of intraocular pressure which treats or prevents the ophthalmic disorders. Among the disorders are intraocular hypertension, glaucoma, low tension glaucoma, age-related macular degeneration (AMD), macular edema, and diabetic retinopathy.As glucocorticoids and mineralocorticoids also cause the retention of ions, such as sodium and potassium, where aldosterone receptors are located, aldosterone receptor antagonists that contain a 9,11-epoxy moiety, such as eplerenone, also can be administered to modulate the intraocular concentration of ions. Thus, aldosterone receptor antagonists can be administered to maintain an intraocular ionic environment that is beneficial to intraocular cell survival. Excerpt(s): This application is a complete application based on U.S. provisional application Serial No. 60/341,033, filed Dec. 12, 2001 and the entire disclosure of which is incorporated herein by reference. The present invention relates to novel methods for the treatment or prevention of glaucoma, ocular hypertension, and other ophthalmic disorders exhibiting elevated intraocular pressure, as well as ocular disorders characterized by retinal neurodegeneration or edema including glaucoma, diabetic retinopathy, and adult macular degeneration with one or more epoxy-steroidal aldosterone receptor antagonists. Glaucoma is a group of diseases that can lead to damage to the eye's optic nerve and result in blindness. The optic nerve connects the retina, the light-sensitive layer of nerve cells at the back of the eye, with the brain. A healthy optic nerve is necessary for good vision.

Patents 183

Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

N-aryl (thio) anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors Inventor(s): Altmann, Karl-Heinz; (Reinach, CH), Bold, Guido; (Gipf-Oberfrick, CH), Ferrari, Stefano; (Muttenz, CH), Furet, Pascal; (Thann, FR), Haberey, Martin; (Berlin, DE), Hofmann, Francesco; (Bottmingen, CH), Huth, Andreas; (Berlin, DE), Kruger, Martin; (Berlin, DE), Manley, Paul William; (Arlesheim, CH), Menrad, Andreas; (Oranienburg, DE), Mestan, Jurgen; (Denzlingen, DE), Seidelmann, Dieter; (Berlin, DE), Thierauch, Karl-Heinz; (Berlin, DE), Wood, Jeanette Marjorie; (Biel-Benken, CH) Correspondence: Thomas Hoxie; Novartis Corporation; Patent And Trademark Dept; 564 Morris Avenue; Summit; NJ; 079011027 Patent Application Number: 20030064992 Date filed: June 26, 2002 Abstract: 1Described are compunds of formula (I), wherein W is O or S; X is NR.sub.8; Y is CR.sub.9R.sub.10--(CH.sub.2)n wherein R.sub.9 and R.sub.10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO.sub.2; R.sub.1 is aryl; R.sub.2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R.sub.2 cannot represent 2-phthalimidyl, and in case of Y=SO.sub.2 cannot represent 2,1,3benzothiadiazol-4-yl; any of R.sub.3, R.sub.4, R.sub.5 and R.sub.6, independently of the other, is H or a substituent other than hydrogen; and R.sub.7 and R.sub.8, independently of each other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration. Excerpt(s): The invention relates to new benzamide derivatives, processes for the preparation thereof, the application thereof in a process for the treatment of the human or animal body, the use thereof--alone or in combination with one or more other pharmaceutically active compounds--for the treatment especially of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration; a method for the treatment of such a disease in animals, especially in humans, and the use of such a compound--alone or in combination With one or more other pharmaceutically active compounds--for manufacture of a pharmaceutical preparation (medicament) for the treatment of a neoplastic disease, of retinopathy and age-related macular degeneration. Certain diseases are known to be associated with deregulated angiogenesis, for example diseases caused by ocular neovascularisation, such as retinopathies (including diabetic retinopathy), age-related macula degeneration, psoriasis, haemangioblastoma, haemangioma, arteriosclerosis, an inflammatory disease, such as a rheumatoid or rheumatic inflammatory disease, especially arthritis, such as rheumatoid arthritis, or other chronic inflammatory disorders, such as chronic asthma, arterial or post-transplantational atherosclerosis, endometriosis, and especially neoplastic diseases, for example so-called solid tumours and liquid tumours (such as leucemias). According to recent findings, at the centre of the network regulating the growth and differentiation of the vascular system and its components, both during embryonic development and normal growth and in a wide number of pathological

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anomalies and diseases, lies the angiogenic factor known as "Vascular Endothelial Growth Factor" (=VGEF; originally termed "Vascular Permeability Factor", =VPF), along with its cellular receptors (see Breier, G., et al., Trends in Cell Biology 6, 454-6 [1996] and references cited therein). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel integrin ligand ITGL-TSP Inventor(s): Fornwald, James A.; (Norristown, PA), Hastings, Gregg A.; (Westlake Village, CA), Jonak, Zdenka L.; (Devon, PA), Terrett, Jonathon A.; (Oxfordshire, GB), Trulli, Stephen H.; (Havertown, PA) Correspondence: Human Genome Sciences Inc; 9410 Key West Avenue; Rockville; MD; 20850 Patent Application Number: 20030166065 Date filed: April 4, 2002 Abstract: ITGL-TSP polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing ITGL-TSP polypeptides and polynucleotides in the design of protocols for the treatment of, angiogenic diseases (cancer, cancer metastasis, chronic inflammatory disorders, rheumatoid arthritis, atherosclerosis, macular degeneration, diabetic retinopathy), restenosis, Alzheimer's disease and tissue remodeling, among others, and diagnostic assays for such conditions. Excerpt(s): This application is a continuation of U.S. patent application Ser. No. 08/845,496, filed Apr. 24, 1997, which is herein incorporated by reference. This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to thrombospondin-metalloproteinase family, hereinafter referred to as ITGL-TSP. The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. ITGL-TSP is a novel thrombospondin (metalloproteinase)-like gene which could have multifunctional activity in normal and disease states. The homology to the thrombospondin type 1 (TSP-1) would "predict" that ITGL-TSP could have similar functions such as TSP-1. TSP-1 modulates aggregation of platelets, formation and lysis of fibrin, adhesion and migration of cells and progression of cells through the growth cycle. TSP-1 is implicated as a potential regulator of tumor growth and metastasis. Conflicting observations suggest that overexpression of TSP-1 causes "increased or suppressed" tumor growth. TSP-1 is a homotrimer with different functional domains, some of which serve as receptor recognizing regions. One of the important functions has been its ability to bind to integrins, such as a Vb3, aIIbb3 and other unknown integrin receptors. Integrins are a large family of cell surface receptors that mediate cell to cell as well as cell to matrix adhesion. Structurally, integrins consist of a heterodimer of an a and b chain. Each subunit has a large N-terminal extracellular domain followed by a transmembrane domain and a short C-terminal cytoplasmic region. Some receptors share a common b chain while having different a chains. ITGL-TSP could be a such novel ligand which could play an important role in different diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Novel retina-specific human proteins C7orf9, C12orf7, MPP4 and F379 Inventor(s): Stoehr, Heidi; (Wuerzburg, DE), Weber, Bernard H. F.; (Wuerzburg, DE) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030054446 Date filed: November 29, 2001 Abstract: The present invention relates to the novel human retina-specific proteins called C7orf9, C12orf7, MPP4 and F379, and isolated nucleic acid molecules encoding said proteins. Also provided are vectors, host cells, antibodies and recombinant methods for producing these human proteins. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating macular degeneration, e.g. AMD. Excerpt(s): The present invention relates to gene expression in human retinal tissue and particularly to the novel retina-specific proteins C7orf9, C12orf7, MPP4 and F379 associated with macular degeneration including age-related macular degeneration (AMD) and the genes encoding C7orf9, C12orf7, MPP4 and F379. First described in 1855, age-related macular degeneration (AMD) is now recognized as the most common cause of visual morbidity in the developed world The prevalence of AMD in persons over 52 was found to be 9% increasing to more than 25% in persons over the age of 75. Projected estimates indicate that by the year 2020 as many as 7.5 million individuals over 65 years may suffer from central vision loss due to AMD. As the population of older people in industrialized countries increases, the associated social and economic consequences of AMD are destined to increase in the next millenium unless preventive or therapeutic treatments can be devised. Histologically, an increasing accumulation of yellowish lipofuscin-like particles within the retinal pigment epithelium (RPE) can be observed with age. This likely represents an early stage in the evolution of AMD which is followed by secondary complications frequently associated with loss of visual acuity. It is thought that the lipofuscin-like deposits represent remnants of undigested phagocytosed photoreceptor outer segment membranes which, in the normal physiological processes, are excreted basally through Bruch's membrane into the choriocapillaris. Over time, incomplete digestion and accumulation of lipofuscin-like particles affect Bruch's membrane and lead to its progressive destruction as seen by electron microscopy as an abnormal thickening of the inner collagenous layer of the membrane. The deposits in the RPE and Bruch's membrane consist largely of lipids although their exact composition may vary between individuals with some deposits revealing more polar phospholipids while others contain predominantly apolar neutral lipids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Nucleic acid and amino acid sequences for ATP-binding cassette transporter and methods of screening for agents that modify ATP-binding cassette transporter Inventor(s): Allikmets, Rando; (Frederick, MD), Anderson, Kent L.; (Houston, TX), Dean, Michael; (Frederick, MD), Leppert, Mark; (Salt Lake City, UT), Lewis, Richard A.; (Houston, TX), Li, Yixin; (Houston, TX), Lupski, James R.; (Houston, TX), Nathans, Jeremy; (Baltimore, MD), Rattner, Amir; (Baltimore, MD), Shroyer, Noah F.; (Houston, TX), Singh, Nanda; (Salt Lake City, UT), Smallwood, Philip; (Woodbine, MD), Sun, Hui; (Baltimore, MD) Correspondence: Woodcock Washburn Llp; One Liberty Place, 46th Floor; 1650 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20030162276 Date filed: January 10, 2003 Abstract: The present invention provides nucleic acid and amino acid sequences of an ATP binding cassette transporter and mutated sequences thereof associated with macular degeneration. Methods of detecting agents that modify ATP-binding cassette transporter comprising combining purified ATP binding cassette transporter and at least one agent suspected of modifying the ATP binding cassette transporter an observing a change in at least one characteristic associated with ATP binding cassette transporter. Methods of detecting macular degeneration is also embodied by the present invention. Excerpt(s): This application claims priority to U.S. provisional application serial No. 60/039,388, filed Feb. 27, 1997. Members of the superfamily of mammalian ATP binding cassette (ABC) transporters are being considered as possible candidates for human disease phenotypes. The ABC superfamily includes genes whose products are transmembrane proteins involved in energy-dependent transport of a wide spectrum of substrates across membranes (Childs and Ling, 1994; Dean and Allikmets, 1995). Many disease-causing members of this superfamily result in defects in the transport of specific substrates (CFTR, Riordan et al., 1989; ALD, Mosser et al., 1993; SUR, Thomas et al., 1995; PMP70, Shimozawa et al., 1992; TAP2, de la Salle et al., 1994). In eukaryotes, ABC genes encode typically four domains that include two conserved ATP-binding domains (ATP) and two domains with multiple transmembrane (TM) segments (Hyde et al. 1996). The ATP-binding domains of ABC genes contain motifs of characteristic conserved residues (Walker A and B motifs) spaced by 90-120 amino acids. Both this conserved spacing and the "Signature" or "C" motif just upstream of the Walker B site distinguish members of the ABC superfamily from other ATP-binding proteins (Hyde et al., 1990; Michaelis and Berkower, 1995). These features have allowed the isolation of new ABC genes by hybridization, degenerate PCR, and inspection of DNA sequence databases (Allikmets et al., 1993, 1995; Dean et al., 1994; Luciani et al., 1994). The characterization of twenty-one new members of the ABC superfamily may permit characterization and functions assigned to these genes by determining their map locations and their patterns of expression (Allikmets et al., 1996). That many known ABC genes are involved in inherited human diseases suggests that some of these new loci will also encode proteins mutated in specific genetic disorders. Despite regionally localizing a gene by mapping, the determination of the precise localization and sequence of one gene nonetheless requires choosing the certain gene from about 250 genes, four to about five million base pairs, from within the regionally localized chromosomal site. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 187

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Objective system and method for evaluating ocular changes including assessment of macular integrity and function Inventor(s): Grant, Alan; (Chevy Chase, MD) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030002014 Date filed: July 2, 2001 Abstract: A system and method for objectively testing for ocular changes including agerelated macular degeneration through reliance on involuntary physical reactions such as the fixation reflex and optokinetic nystagmus. A narrow band of visible blue light is beamed at the patient's eye through alternate apertures in a mask which are separated by a relatively small angle of subtendance at the entrance pupil. In the presence of a healthy macula, the blue light is filtered out and the fixation reflex is absent. Conversely, if the macula is in the process of degenerating by the progressive loss of protective pigments, then the impinging of the narrow band of visible blue light upon the macula, via the alternate apertures, will evoke the fixation reflex. Excerpt(s): The present invention is related to the field of ocular health, disease and degeneration and, more particularly, to a noninvasive system and objective method for analyzing macular function and thereby detecting macular changes and degradations, which may be predictive of future age-related macular degeneration. Human longevity is extending, and we are increasingly subject to adverse physiological changes which are detrimental to our well-being and independence. Loss of visual acuity, which may or may not lead ultimately to blindness, can be debilitating. The macula lutea, a small area lying slightly lateral to the center of the retina, represents the region of maximum visual acuity in the human eye. While many age-related ocular changes such as cataract formation, adult-onset diabetes, and glaucoma can be reasonably well-managed so that visual self-sufficiency can be maintained, Age-related Macular Degeneration (AMD) impacting the macula lutea is progressively the most debilitating exception. Evaluation of the macula lutea has traditionally been limited to subjective testing. By definition, subjective testing is flawed and individually anecdotal, due to total reliance on patient responses. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Substituted benzofurans and benzothiophenes, methods of making and methods of use as integrin antagonists Inventor(s): Anaclerio, Beth M.; (New Castle, DE), Marder, Victor J.; (Los Angeles, CA), Sanchez, Juan Jose Marugan; (Downingtown, PA), U'Prichard, David C.; (Philadelphia, PA) Correspondence: Sterne, Kessler, Goldstein & Fox Pllc; 1100 New York Avenue, N.W., Suite 600; Washington; DC; 20005-3934; US Patent Application Number: 20030018064 Date filed: April 26, 2002 Abstract: The present invention relates to novel substituted benzofurans and benzothiophenes compounds that are antagonists of alpha V (.alpha.v) integrins, for example.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5 integrins, their

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pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula I: 1where R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, m, n, i, j and k are defined herein. Excerpt(s): This application claims priority to Provisional application No. 60/324,516, filed Oct. 26, 2001, and also claims priority to Provisional application No. 60/286,532, filed on Apr. 27, 2001. The present invention relates to novel substituted benzofurans and benzothiophenes that are antagonists of alpha V (.alpha.v) integrins, for example.alpha.sub.v.beta.sub.3 and.alpha.sub.v.beta.sub.5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. Integrins are cell surface glycoprotein receptors which bind extracellular matrix proteins and mediate cell-cell and cell-extracellular matrix interactions (generally referred to as cell adhesion events) (Hynes, R. O., Cell 69:11-25 (1992)). These receptors are composed of noncovalently associated alpha (.alpha.) and beta (.beta.) chains which combine to give a variety of heterodimeric proteins with distinct cellular and adhesive specificities (Albeda, S. M., Lab. Invest. 68:4-14 (1993)). Recent studies have implicated integrins in the regulation of cellular adhesion, migration, invasion, proliferation, apoptosis and gene expression (Albeda, S. M., Lab. Invest. 68:4-14 (1993); Juliano, R., Cancer Met. Rev. 13:25-30 (1994); Ruoslahti, E. and Reed, J. C., Cell 77:477-478 (1994); and Ruoslahti, E. and Giancotti, F. G., Cancer Cells 1:119-126 (1989)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

System and method for full field oscillating stimulus perimeter Inventor(s): Stewart, Jeffrey L.; (Greenwich, CT) Correspondence: John DE LA Rosa; Suite 2211; 67 Wall Street; New York; NY; 10005; US Patent Application Number: 20030081176 Date filed: October 1, 2001 Abstract: A novel visual field test utilizing oscillating visual stimuli is proposed, which may be used to diagnose for eye disorders, such as glaucoma or macular degeneration. Such visual stimuli oscillate in color, polarity, saturation, luminance or intensity. Preferably, the visual test pattern consists of oscillating visual stimuli arranged in a pattern, such as a repeating or grid pattern, covering substantially all of the field of vision being tested. And, may include the use of frequency doubling visual stimuli. In use, the visual field test pattern is positioned in front of the patient so as to cover substantially all of the field of vision being tested, typically about a solid angle of 40.degree. or more. The eye under examination is fixated, and the patient asked to indicate areas where the oscillating visual stimuli are dissimilar, such as by outlining those areas different from the rest of the visual field test pattern. This procedure may be repeated for different contrast, saturation, or luminance levels, corresponding to varying degrees of visual sensitivity levels. Areas of dissimilarity correspond to visual field defects. The characteristic locations of the areas of dissimilarity for a particular sensitivity setting will allow clinicians not only to diagnose, but also to determine the severity of the eye disorder.

Patents 189

Excerpt(s): The present invention relates to a visual test system and method for testing the functioning of different parts of the retina and other potions of the visual pathway. A large number of degenerative eye disorders, such as glaucoma and macular degeneration, may be detected by evaluating a patient's visual field, such as through perimetry and campimetry. While the patient's eye is fixated, such visual tests present discrete light stimuli in the patient's field of vision, and then monitor the patient's response to the stimuli, allowing a mapping of the visual field to be obtained. Visual field tests employing test patterns have also been developed for measuring a patient's visual field. One such visual test uses a so-called "Amsler grid" consisting of equally spaced, parallel, horizontal and vertical lines. In use, the grid is positioned about 28-30 cm in front of the patient. With one eye covered, the other eye is fixated on a central point positioned in the grid, such as a dot. The patient is then asked to indicate areas of distortion in the grid by, for example, drawing an outline around the areas of grid distortion, such as, missing squares or wavy lines. Over time, the patient is again asked to note any changes that occur in the severity or location of the grid distortion, typically on a daily or weekly basis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Telomere-encoding synthetic DNA nanocircles, and their use for the elongation of telomere repeats Inventor(s): Kool, Eric T.; (Stanford, CA) Correspondence: Howrey Simon Arnold & White Llp; 750 Bering Drive; Houston; TX; 77057; US Patent Application Number: 20030148988 Date filed: January 3, 2003 Abstract: Telomere-encoding nucleic acid nanocircles, methods for their preparation, and methods for their use are disclosed. The nanocircles can be constructed containing multiple repeats of the complement of telomere repeat sequences. The telomereencoding nanocircles are useful for extending telomeres both in vitro and in vivo, for treating macular degeneration, the effects of skin aging, liver degeneration, and cancer. The nanocircles are further useful for treating cell cultures to produce long-lived noncancerous cell populations. This use has wide applicability in scientific research, tissue engineering, and transplantation. Excerpt(s): The present application claims priority to U.S. Provisional Patent Application Serial No. 60/345,056 filed Jan. 4, 2002, the contents of all of which are incorporated herein by reference. The invention relates to compositions and methods for the extension of telomere repeat sequences and, more specifically, to the use of synthetic nucleic acid nanocircles for the extension of telomere repeat sequences. The invention further relates to synthetic, diagnostic, and therapeutic uses for the nanocircles. The many potential uses of telomere-encoding nanocircles include their use to enhance the lifespan of non-cancerous cell populations in culture, to treat macular degeneration, to treat skin aging, to treat liver degeneration, and to treat cancer. Additionally, nanocircles can be used to elongate telomeres in vitro, to add synthetic telomeres onto chemicals or biomolecules having a telomere primer, and to add detectable or modified bases into a telomere. Human cell populations typically have a finite lifetime, dividing a number of times before entering a nondividing phase called "replicative senescence". Human chromosomes are capped with repeated sequences called "telomeres". Human telomeres consist of up to about 2500 repeats of the sequence 5'-TTAGGG-3' (SEQ ID NO:1).

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Telomeres in normal non-cancerous cells shorten each time that a cell divides. This has been viewed as a type of `clock`, helping to determine the lifespan of a cell population. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Topical treatment of ocular hypertension, glaucoma, ischemic retinopathy and agerelated macular degeneration with ophthalmic formulation of dopamine antagonists Inventor(s): Chiou, George C.Y.; (College Station, TX) Correspondence: Morrison & Foerster Llp; 755 Page Mill RD; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030069232 Date filed: February 28, 2001 Abstract: This invention provides ocular formulations comprising an ocular drug and a carboxylic acid in an amount sufficient to maintain the pH of the formulation from about 4.5 to about 7.5. The ocular drug may be a dopamine antagonist and the acid may be lactic acid, citric acid or tartaric acid. In some aspects, the pH of the formulation is about 5.5 The ocular formulations of this invention provide enhanced bioavailability which results in increased drug concentrations across the cornea and in the eye ball, i.e., aqueous humor and intraocular organs and chambers. Moreover, the present formulations are non-irritating when applied topically and have a shelf-life of at least fourteen days at 25.degree. C. Methods are also provided to increase ocular blood flow by using present ocular formulations comprising dopamine antagonists or other drugs for the prevention and treatment of ocular hypertension, glaucoma, ischemic retinopathy and age-related macular degeneration (AMD). Excerpt(s): The present invention relates generally to ocular formulations and methods for using those formulations to improve blood flow to the retina and choroid to halt or reverse the course of visual deterioration. Accordingly, this invention transcends the related disciplines of pharmaceutical sciences, ocular pharmacology and medicine. Several potential drugs have been developed with high anticipation of treating various eye diseases, yet only a few of those potential drugs have reached the clinics because of the problems of drug delivery. Ocular drug delivery faces three major difficulties: first, the ocular bioavailability of the drug is often poor because the drug needs to cross the cornea to enter the eye ball, i.e., the aqueous humor and other interior anatomical organs of the eye; second, very often, the drug formulation is irritable when applied topically to the eye; and third, the ocular formulations are very unstable, i.e., have a short shelf-life, in the order of a few days to few weeks. For example, most, if not all dopamine antagonists do not dissolve in plain aqueous medium and, as a result, their non-aqueous formulations often produce severe eye irritation. Various absorption enhancers and antiirritants have been proposed in the prior art to overcome these difficulties. However, the search for a successful resolution to the problem continues. Accordingly, there is a need for stable ocular formulations that enhance the ocular bioavailability of a drug with reduced ocular irritation when administered topically. As the following description illustrates, the present invention meets this need. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Treatment of disease states characterized by excessive or inappropriate angiogenesis Inventor(s): Payne, J. Donald; (Spring, TX), West, Jennifer L.; (Pearland, TX) Correspondence: Eric P. Mirabel; 3783 Darcus; Houston; TX; 77005; US Patent Application Number: 20030118657 Date filed: December 3, 2002 Abstract: Disclosed is a method for reducing excessive or inappropriate neovasculature, including nevasculature in the eye which interferes with or has potential to interfere with vision, for example, that associated with diabetic retinopathy or macular degeneration. The regions of the neovasculature are targeted with nanoparticles, including metal nanoshells, which are then irradiated, preferably with a laser, to heat them and ablate the undesired blood vessels. The nanoparticles are targeted to the neovasculature by linking them with a targeting agent, including, for example, antibodies, antibody fragments, receptor binding proteins or other proteins or molecules including growth factors. Excerpt(s): This Application claims the benefit of U.S. Provisional Application No. 60/336,824, filed on Dec. 3, 2001. Certain disease states and conditions, including macular degeneration, diabetic retinopathy, cancer and healing wounds, are characterized by excessive or inappropriate angiogenesis. Macular degeneration and diabetic retinopathy can both lead to blindness or deterioration of vision. In both these conditions, new blood vessels which proliferate in the retina are the main cause of vision impairment. In cancer, the tumor promotes the growth of new blood vessels to support the growth of the tumor. Angiogenesis arising in connection with wounds may impair healing. Macular degeneration relates to a breakdown of the macula, the light-sensitive part of the retina responsible for the sharp, direct vision needed for activities including reading or driving. Macular degeneration is more common in people over age 65, and whites and females are at highest risk. Most cases of macular degeneration are related to aging (age-related macular degeneration), but it also can occur as a side effect of some drugs, and it appears to run in families. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Tyrosine kinase inhibitors Inventor(s): Bilodeau, Mark T.; (Lansdale, PA), Hartman, George D.; (Lansdale, PA), Hungate, Randall W.; (Newbury Park, CA), Manley, Peter J.; (Harleysville, PA), Rodman, Leonard; (New York, NY) Correspondence: Merck & CO., INC.; Patent Department; P.O. Box 2000 - Ry60-30; Rahway; NJ; 07065-0907; US Patent Application Number: 20030064996 Date filed: February 1, 2002 Excerpt(s): This application claims priority under 35 U.S.C.sctn.119(e) from U.S. Provisional Application 60/153,348, filed Sep. 10.sup.th, 1999. The present invention relates to compounds which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent diseases and conditions, such as angiogenesis, cancer, tumor growth, atherosclerosis, age related macular degeneration, diabetic retinopathy, inflammatory diseases, and the like in mammals. Tyrosine kinases are a

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class of enzymes that catalyze the transfer of the terminal phosphate of adenosine triphosphate to tyrosine residues in protein substrates. Tyrosine kinases are believed, by way of substrate phosphorylation, to play critical roles in signal transduction for a number of cell functions. Though the exact mechanisms of signal transduction is still unclear, tyrosine kinases have been shown to be important contributing factors in cell proliferation, carcinogenesis and cell differentiation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of melanin for inhibition of angiogenesis and macular degeneration Inventor(s): D'Amato, Robert J.; (Lexington, MA) Correspondence: John S. Pratt, Esq; Kilpatrick Stockton, Llp; 1100 Peachtree Street; Suite 2800; Atlanta; GA; 30309; US Patent Application Number: 20030096735 Date filed: January 9, 2003 Abstract: Composition and methods of using melanin, or melanin-promoting compounds, for inhibiting angiogenesis to treat angiogenesis-dependent diseases, such as macular degeneration and cancer. Excerpt(s): This application relates to a inhibitor of angiogenesis useful for treating angiogenesis-related diseases, such as macular degeneration and angiogenesisdependent cancers. The invention further relates to novel pharmaceutical compositions and methods for treating and curing macular degeneration, and other angiogenesisdependent diseases. As used herein, the term "angiogenesis" means the generation of new blood vessels into a tissue or organ. Under normal physiological conditions, humans or animals only undergo angiogenesis in very specific restricted situations. For example, angiogenesis is normally observed in wound healing, fetal and embryonal development and formation of the corpus luteum, endometrium and placenta. The control of angiogenesis is a highly regulated system of angiogenic stimulators and inhibitors. The control of angiogenesis has been found to be altered in certain disease states and, in many cases, the pathological damage associated with the disease is related to the uncontrolled angiogenesis. Both controlled and uncontrolled angiogenesis are thought to proceed in a similar manner. Endothelial cells and pericytes, surrounded by a basement membrane, form capillary blood vessels. Angiogenesis begins with the erosion of the basement membrane by enzymes released by endothelial cells and leukocytes. The endothelial cells, which line the lumen of blood vessels, then protrude through the basement membrane. Angiogenic stimulants induce the endothelial cells to migrate through the eroded basement membrane. The migrating cells form a "sprout" off the parent blood vessel, where the endothelial cells undergo mitosis and proliferate. The endothelial sprouts merge with each other to form capillary loops, creating the new blood vessel. In the disease state, prevention of angiogenesis could avert the damage caused by the invasion of the new microvascular system. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Vision through photodynamic therapy of the eye Inventor(s): Fsadni, Mario; (Buelach, CH), Huber, Gustav; (Zurich, CH), Levy, Julia; (Vancouver, CA), Strong, H. Andrew; (North Van, CA) Correspondence: Morrison & Foerster Llp; 3811 Valley Centre Drive; Suite 500; San Diego; CA; 92130-2332; US Patent Application Number: 20030149012 Date filed: March 7, 2003 Abstract: Photodynamic therapy of conditions of the eye, especially those conditions characterized by unwanted neovasculature, such as age-related macular degeneration, results in enhanced visual acuity for treated subjects. Excerpt(s): The invention relates to a method to improve visual acuity by administering photodynamic therapy (PDT) to the eye. Loss of visual acuity is a common problem associated with aging and with various conditions of the eye. Particularly troublesome is the development of unwanted neovascularization in the cornea, retina or choroid. Choroidal neovascularization leads to hemorrhage and fibrosis, with resultant visual loss in a number of recognized eye diseases, including macular degeneration, ocular histoplasmosis syndrome, myopia, and inflammatory diseases. Age-related macular degeneration (AMD) is the leading cause of new blindness in the elderly, and choroidal neovascularization is responsible for 80% of the severe visual loss in patients with this disease. Although the natural history of the disease is eventual quiescence and regression of the neovascularization process, this usually occurs at the cost of sub-retinal fibrosis and vision loss. Current treatment of AMD relies on occlusion of the blood vessels using laser photocoagulation. However, such treatment requires thermal destruction of the neovascular tissue, and is accompanied by full-thickness retinal damage, as well as damage to medium and large choroidal vessels. Further, the subject is left with an atrophic scar and visual scotoma. Moreover, recurrences are common, and visual prognosis is poor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Zeaxanthin formulations for human ingestion Inventor(s): Garnett, Kevin M.; (Morristown, NJ), Gierhart, Dennis L.; (Chesterfield, MO), Guerra-Santos, Luis H.; (Ballwin, MO) Correspondence: Patrick D. Kelly; 11939 Manchester #403; ST. Louis; MO; 63131; US Patent Application Number: 20030108598 Date filed: December 17, 2002 Abstract: Preparations are disclosed containing the 3R-3'R stereoisomer of zeaxanthin, packaged for oral ingestion by humans as a therapeutic drug or nutritional supplement. Zeaxanthin is a yellow carotenoid pigment found in the macula (in the center of the human retina), which helps protect retinal cells against phototoxic damage. The R-R stereoisomer can be prepared by fermenting cells, such as Flavobacterium multivorum (ATCC 55238), which do not create any detectable quantity of the undesired and potentially toxic S-S or S-R isomers, and which do not synthesize any other carotenoids. The R-R isomer can be concentrated, in large quantities and at low cost, into a viscous oily fluid containing about 5 to 20% zeaxanthin, by means of a simple solvent extraction process. This oily fluid can be mixed with a carrier such as vegetable oil and enclosed

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within a digestible capsule, comparable to a conventional capsule containing Vitamin E. It can also be prepared in a microencapsulated granular formulation, and/or in a tablet form with an enteric coating. Alternately, a zeaxanthin fluid can be added to various types of foods, such as margarine, dairy products, syrup, cookie dough, and meat preparations that are not subjected to harsh cooking. Such processing can be used to create formulations such as ingestible tablets, and particulate formulations that can be added to soups, salads, drinks, or other foods. Preferred stabilizers and anti-oxidants are also disclosed. When consumed by humans in any of these modes, the R-R isomer of zeaxanthin can help treat and prevent macular degeneration, one of the leading causes of blindness and vision loss, especially among the elderly. Excerpt(s): This is a continuation of U.S. patent application Ser. No. 09/699,985, filed on Oct. 27, 2000, which requested reissuance of U.S. Pat. No. 5,827,652, which arose from application Ser. No. 08/551,153, filed on Oct. 31, 1995. This invention is in the field of pharmacology, and relates to human use of a yellow pigment called zeaxanthin (ZX) in preventing or treating macular degeneration, a disease which damages retinal tissue and causes blindness. A related U.S. Pat. No. 5,854,015 ("Method of Making Pure 3R-3'R Stereoisomer of Zeaxanthin for Human Ingestion", assigned to the same assignee herein) contains a fairly extensive discussion of retinal physiology and carotenoid chemistry. The contents of that patent are incorporated herein by reference. Although that Background information will not be repeated herein in its entirety, a brief overview is provided in the next paragraphs, to help introduce and explain this invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with macular degeneration, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “macular degeneration” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on macular degeneration. You can also use this procedure to view pending patent applications concerning macular degeneration. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 7. BOOKS ON MACULAR DEGENERATION Overview This chapter provides bibliographic book references relating to macular degeneration. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on macular degeneration include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “macular degeneration” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on macular degeneration: •

Live Now, Age Later: Proven Ways to Slow Down the Clock Source: New York, NY: Warner Books. 1999. 398 p. Contact: Available from Warner Books. 1271 Avenue of the Americas, New York, NY 10020. (800) 759-0190. E-mail: [email protected]. Website: www.twbookmark.com. PRICE: $7.99 plus shipping and handling. Summary: This book offers practical strategies and healthy living advice for people who want to slow down their own aging process. The book is written in casual language with an emphasis on explaining medical and health issues for the general public. Twenty chapters cover Alzheimer's disease, cancer, constipation, depression, hearing loss, heart attacks, erectile dysfunction (impotence), insomnia, libido, menopause, osteoarthritis, osteoporosis, prostate enlargement, aging skin, stroke, diminished taste and smell, tinnitus, tooth loss, and loss of vision (macular degeneration, cataracts, glaucoma). Each

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chapter reviews the topic in question, risk factors, the type of symptoms that can be expected, diagnostic tests that are used to confirm the problem, treatment options, and prognosis. A final section offers general health guidelines that focus on the importance of positive thinking and healthy lifestyle choices. A subject index concludes the book.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “macular degeneration” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “macular degeneration” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “macular degeneration” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Age-Related Macular Degeneration (2003); ISBN: 3540064931; http://www.amazon.com/exec/obidos/ASIN/3540064931/icongroupinterna

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Age-Related Macular Degeneration by Jennifer I. Lim (Editor) (2002); ISBN: 082470682X; http://www.amazon.com/exec/obidos/ASIN/082470682X/icongroupinterna

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Age-Related Macular Degeneration by Stuart L. Fine (Editor), et al (1999); ISBN: 0323002005; http://www.amazon.com/exec/obidos/ASIN/0323002005/icongroupinterna

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Age-Related Macular Degeneration by W. E. Aberti (Editor), et al; ISBN: 3540666435; http://www.amazon.com/exec/obidos/ASIN/3540666435/icongroupinterna

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Age-related Macular Degeneration (AMD) and Lutein: Assessing the Evidence (Round Table Series (RTS)) by Steven Pratt (Editor) (2002); ISBN: 1853155004; http://www.amazon.com/exec/obidos/ASIN/1853155004/icongroupinterna

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Age-related macular degeneration : information for patients (SuDoc HE 20.3752:AG 3/999) by U.S. Dept of Health and Human Services; ISBN: B00010YT8S; http://www.amazon.com/exec/obidos/ASIN/B00010YT8S/icongroupinterna

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Age-Related Macular Degeneration: Management & Rehabilitation by Jan E. LovieKitchin, Ken Bowman; ISBN: 0750696842; http://www.amazon.com/exec/obidos/ASIN/0750696842/icongroupinterna

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Age-Related Macular Degeneration: Principles and Practice by G. Robert Hampton, et al; ISBN: 088167916X; http://www.amazon.com/exec/obidos/ASIN/088167916X/icongroupinterna

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Bilberry & Lutein: The Vision Enhancers! Protect Against Cataracts, MacUlar Degeneration, Glaucoma, Retinopathy & Other Health Problems (Health lear by Beth M. Ley; ISBN: 189076616X; http://www.amazon.com/exec/obidos/ASIN/189076616X/icongroupinterna

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Conquering Macular Degeneration: The Latest Breakthroughs and Treatments by Edward L. Paul (2002); ISBN: 1553697928; http://www.amazon.com/exec/obidos/ASIN/1553697928/icongroupinterna

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Coping with Macular Degeneration [LARGE PRINT] by Bert Silverman, et al; ISBN: 0965947300; http://www.amazon.com/exec/obidos/ASIN/0965947300/icongroupinterna

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Coping with Macular Degeneration: A Guide for Patients and Families to Understanding and Living with Degenerative Vision Disorder by Ira Mark Price, et al; ISBN: 0895299968; http://www.amazon.com/exec/obidos/ASIN/0895299968/icongroupinterna

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Don't lose sight of age-related macular degeneration : information for people at risk (SuDoc HE 20.3752:AG 3/2) by U.S. Dept of Health and Human Services; ISBN: B00010FOQ4; http://www.amazon.com/exec/obidos/ASIN/B00010FOQ4/icongroupinterna

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Focus on Macular Degeneration Research by O. R. Ioseliani (Editor) (2004); ISBN: 1590338987; http://www.amazon.com/exec/obidos/ASIN/1590338987/icongroupinterna

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Greens Are Good for You!: How Green Power Protects You Against Heart Disease, Cancer, Diabetes, Macular Degeneration, Poor Night Vision, Senile Dementia, Liver Disease, fatigue by Tony O'Donnell; ISBN: 1591200369; http://www.amazon.com/exec/obidos/ASIN/1591200369/icongroupinterna

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Healing the Eye the Natural Way: Alternate Medicine and Macular Degeneration by Edward C., M.D. Kondrot, et al; ISBN: 1556434022; http://www.amazon.com/exec/obidos/ASIN/1556434022/icongroupinterna

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Living Well With Macular Degeneration: Practical Tips and Essential Information by Bruce, Dr. Rosenthal, et al (2001); ISBN: 0451202643; http://www.amazon.com/exec/obidos/ASIN/0451202643/icongroupinterna

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MacUlar Degeneration by Howard Schatz, H. Richard McDonald; ISBN: 0960810226; http://www.amazon.com/exec/obidos/ASIN/0960810226/icongroupinterna

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Macular Degeneration : How to Recognize Symptoms, Understand Treatment Options and Live Protectively With Vision Loss by Betty Wason, et al (1998); ISBN: 0897932390; http://www.amazon.com/exec/obidos/ASIN/0897932390/icongroupinterna

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Macular Degeneration: Overview and Abstracts by O. R. Ioseliani (Editor) (2002); ISBN: 1590334647; http://www.amazon.com/exec/obidos/ASIN/1590334647/icongroupinterna

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Macular Degeneration: The Complete Guide to Saving and Maximizing Your Sight by Lylas G. Mogk, Marja Mogk; ISBN: 0345457110; http://www.amazon.com/exec/obidos/ASIN/0345457110/icongroupinterna

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Macular Degeneration: The Latest Scientific Discoveries and Treatments for Preserving Your Sight by Robert D'Amato M.D. Ph.D., et al (2000); ISBN: 0802713599; http://www.amazon.com/exec/obidos/ASIN/0802713599/icongroupinterna

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Mayo Clinic on Vision and Eye Health: Practical Answers on Glaucoma, Cataracts, Macular Degeneration & Other Conditions by Helmut Buettner (Editor), Mayo Clinic (2002); ISBN: 1893005208; http://www.amazon.com/exec/obidos/ASIN/1893005208/icongroupinterna

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My Friend, You Are Legally Blind A Writer's Struggle with Macular Degeneration by Charles Champlin; ISBN: 1880284480; http://www.amazon.com/exec/obidos/ASIN/1880284480/icongroupinterna

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Overcoming Macular Degeneration : A Guide to Seeing Beyond the Clouds by Yale Solomon, Jonathan D. Solomon (Contributor) (2000); ISBN: 0380805898; http://www.amazon.com/exec/obidos/ASIN/0380805898/icongroupinterna

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Save Your Sight! : Natural Ways to Prevent and Reverse Macular Degeneration by Michael R Marc R./Rose Rose (Author); ISBN: 0446674028; http://www.amazon.com/exec/obidos/ASIN/0446674028/icongroupinterna

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See Again! : Reversing and Preventing Macular Degeneration by M.D. Alexander Eaton (Author); ISBN: 0609803344; http://www.amazon.com/exec/obidos/ASIN/0609803344/icongroupinterna

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Senile MacUlar Degeneration: Management and Rehabilitation by Kenneth J. Bowman, Jan E. Lovie-Kitchin; ISBN: 0409900079; http://www.amazon.com/exec/obidos/ASIN/0409900079/icongroupinterna

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The Hole in My Vision: An Artist's View of His Own Macular Degeneration by Lee Alien, et al (2000); ISBN: 1572160853; http://www.amazon.com/exec/obidos/ASIN/1572160853/icongroupinterna

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The Macular Degeneration Handbook: Natural Ways to Prevent & Reverse It by Chet Cunningham (1998); ISBN: 1887053115; http://www.amazon.com/exec/obidos/ASIN/1887053115/icongroupinterna

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The Macular Degeneration Source Book: A Guide for Patients and Families by Dr. Bert Glaser, Lester Picker (2001); ISBN: 1886039534; http://www.amazon.com/exec/obidos/ASIN/1886039534/icongroupinterna

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The Official Patient's Sourcebook on Age-Related Macular Degeneration by Icon Health Publications, et al (2002); ISBN: 0597831262; http://www.amazon.com/exec/obidos/ASIN/0597831262/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “macular degeneration” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

A vision impairment of the later years--macular degeneration Author: Dickman, Irving R.; Year: 1987; [New York]: Public Affairs Committee, c1982

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Age-related macular degeneration Author: American Academy of Ophthalmology. Quality of Care Committee. Retina Panel.; Year: 1999; San Francisco, Calif.: The Academy, 1998

11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Age-related macular degeneration [electronic resource]: status of research Author: National Eye Institute.; Year: 2001; [Bethesda, Md.]: The Institute, 1998

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Care of the patient with age-related macular degeneration: reference guide for clinicians Author: American Optometric Association. Consensus Panel on Care of the Patient with Age-Related Macular Degeneration.; Year: 2000; St. Louis, MO: American Optometric Association, c1994 (1996 printing)

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Guidance on the use of photodynamic therapy for age-related macular degeneration Author: National Institute for Clinical Excellence (Great Britain).; Year: 1998; London: National Institute for Clinical Excellence, c2003; ISBN: 1842573799

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Macular degeneration Author: American Academy of Ophthalmology. Quality of Care Committee. Retina Panel.; Year: 1994; San Francisco, CA (P.O. Box 7424, San Francisco 94120-7424): The Academy, [1990]

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Modelling the long-term benefits of photodynamic therapy (PDT) with verteporfin for age-related macular degeneration (AMD) Author: Smith, David H. (David Harold),; Year: 1982; York: University of York, Centre for Health Economics, 2002

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Photodynamic therapy with verteporfin for the treatment of neovascular age-related macular degeneration: a clinical assessment Author: Husereau, Donald Robert.; Year: 2000; Ottawa, Ont.: Canadian Coordinating Office for Health Technology Assessment, [2002]; ISBN: 1894620631

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Senile macular degeneration: January 1980 through October 1984: 112 citations Author: Abrams, Estelle J.; Year: 1991; [Bethesda, Md.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health, [1984]

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Some physiological considerations of hereditary macular degeneration. Author: Steinmetz, Rodney Dunlap,; Year: 2003; [Minneapolis, 1956?]

Chapters on Macular Degeneration In order to find chapters that specifically relate to macular degeneration, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and macular degeneration using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “macular degeneration” (or synonyms) into the “For these words:” box.

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CHAPTER 8. MULTIMEDIA ON MACULAR DEGENERATION Overview In this chapter, we show you how to keep current on multimedia sources of information on macular degeneration. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.

Video Recordings An excellent source of multimedia information on macular degeneration is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “macular degeneration” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “macular degeneration” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on macular degeneration: •

Lasers for Eyes Source: Princeton, NJ: Films for Humanities and Sciences. 1990. Contact: Available from Films for the Humanities and Sciences. P.O. Box 2053, Princeton, NJ 08543-2053. (800) 257-5126. PRICE: $149 (purchase), or $75 (rental), plus 5 percent of total cost for shipping and handling. Order Number FM-2356. Summary: Lasers have revolutionized eye surgery, saving sight where blindness would once have been inevitable and replacing formerly complicated, painful surgery with quicker, safer, less painful, more successful procedures. This patient education video program covers the five principal areas of eye disease in which laser surgery is making important contributions: cataracts, macular degeneration, glaucoma, retinal tears, and diabetic retinopathy. The videotape explains each condition and how it is repaired by laser surgery, identifies the likeliest victims of each condition, and warns of the potential dangers of laser surgery. (AA-M).

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Bibliography: Multimedia on Macular Degeneration The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in macular degeneration (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on macular degeneration: •

A simple and affordable panoramic viewing system for vitreous surgery [videorecording]; Macular translocation for exudative age-related macular degeneration; Juxtapapillary cyst-like lesions of R.P.E. and choroidal origin Source: American Academy of Ophthalmolo; Year: 1999; Format: Videorecording; San Francisco, CA: American Academy of Ophthalmology, c1999

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Age-related macular degeneration [electronic resource]: status of research Source: National Eye Institute; Year: 1998; Format: Electronic resource; [Bethesda, Md.]: The Institute, 1998

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Cytotoxic effects of oxidized cholesterol on RPE cells [videorecording]: a potential mechanism for the pathogenesis of age-related macular degeneration Source: Office of Research Services, Medical Arts and Photography Branch; Year: 2003; Format: Videorecording; [Bethesda, Md.: National Institutes of Health, 2003]

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Macular degeneration [videorecording]: etiology, diagnosis, and treatment Source: with Cynthia J. MacKay; Year: 1989; Format: Videorecording; Secaucus, N.J.: Network for Continuing Medical Education, c1989

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Macular degeneration [videorecording]. Year: 1995; Format: Videorecording; Chicago, Il 1995

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CHAPTER 9. PERIODICALS AND NEWS ON MACULAR DEGENERATION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover macular degeneration.

News Services and Press Releases One of the simplest ways of tracking press releases on macular degeneration is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “macular degeneration” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to macular degeneration. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “macular degeneration” (or synonyms). The following was recently listed in this archive for macular degeneration: •

VEGF antagonist counters age-related macular degeneration Source: Reuters Medical News Date: November 17, 2003

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Vitamins combat age-related macular degeneration Source: Reuters Medical News Date: November 10, 2003

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New crop of antiangiogenic drugs show promise for macular degeneration Source: Reuters Industry Breifing Date: August 06, 2003

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New antiangiogenic drugs show promise for macular degeneration Source: Reuters Medical News Date: August 06, 2003

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Overweight, inactivity increase risk for progression of macular degeneration Source: Reuters Medical News Date: June 23, 2003

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Intravitreal triamcinolone may stabilize exudative age-related macular degeneration Source: Reuters Industry Breifing Date: March 31, 2003

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Vitamin therapy for macular degeneration could save $1.5 billion over decade Source: Reuters Medical News Date: October 22, 2002

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Protein oxidation may play role in age-related macular degeneration Source: Reuters Medical News Date: October 21, 2002

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Depression exacerbates effects of age-related macular degeneration Source: Reuters Medical News Date: August 28, 2002

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Subanalysis identifies candidates for Miravant's macular degeneration therapy Source: Reuters Medical News Date: August 27, 2002

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Translocation of the retina can preserve vision in macular degeneration Source: Reuters Medical News Date: April 29, 2002

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Depression common among adults with advanced macular degeneration Source: Reuters Medical News Date: November 22, 2001

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Worst stages of age-related macular degeneration avoided with antioxidants/zinc Source: Reuters Industry Breifing Date: October 12, 2001

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Vegetable fat consumption may increase risk of macular degeneration Source: Reuters Medical News Date: September 19, 2001

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Specific fat intake linked to risk of advanced age-related macular degeneration Source: Reuters Medical News Date: August 22, 2001

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Alzheimer gene may decrease risk of age-related macular degeneration Source: Reuters Medical News Date: May 03, 2001

Periodicals and News

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Gene defect responsible for two forms of macular degeneration isolated Source: Reuters Industry Breifing Date: January 15, 2001

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Cataract surgery beneficial for patients with macular degeneration Source: Reuters Medical News Date: December 01, 2000

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Medicare to cover photodynamic therapy for wet macular degeneration Source: Reuters Industry Breifing Date: November 10, 2000

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FDA approves Visudyne for age-related macular degeneration Source: Reuters Industry Breifing Date: April 14, 2000

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Gilead licenses potential age-related macular degeneration therapy Source: Reuters Industry Breifing Date: April 07, 2000

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Verteporfin safe, efficacious for prolonged treatment of macular degeneration Source: Reuters Medical News Date: March 29, 2000

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “macular degeneration” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.

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Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “macular degeneration” (or synonyms). If you know the name of a company that is relevant to macular degeneration, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “macular degeneration” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “macular degeneration” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on macular degeneration: •

The Right Foods for Preventing a Leading Cause of Blindness Source: Tufts University Health and Nutrition Letter. 18(12). Special Supplement. February 2001. Contact: 10 High Street, Suite 706, Boston, MA 02110. [email protected] www.healthletter.tufts.edu. Summary: Lutein and zeaxanthin, found in dark green, leafy vegetables, may help reduce risk for macular degeneration, the leading cause of irreversible blindness among older Americans. Dr. Elizabeth Johnson of the Gastrointestinal Nutrition Laboratory at the Tufts Center on Aging fed non-green eaters a small serving of spinach every day for several months to see if the lutein in the spinach actually made it into the bloodstream and from there to the retina. These compounds appear in much higher concentrations in the eye than anywhere else in the body. The study results indicate that the lutein in food does end up in the retina of the eye. Another research project at the Oregon Health Sciences University is underway to determine if people in the early stages of macular degeneration can slow the progress of the disease by eating leafy greens. Already proven ways to reduce the risk for macular degeneration include reducing eye exposure to sunlight, not smoking, drinking in moderation, and (possibly) losing excess weight.

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Academic Periodicals covering Macular Degeneration Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to macular degeneration. In addition to these sources, you can search for articles covering macular degeneration that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 10. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for macular degeneration. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with macular degeneration. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to macular degeneration: Verteporfin •

Systemic - U.S. Brands: Visudyne http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500139.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html The Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “macular degeneration” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “macular degeneration” (or synonyms) into the “For these words:” box. The following is a sample result: •

American Health Assistance Foundation: 1999 Annual Report Source: Rockville, MD: American Health Assistance Foundation. 1999. 48 p. Contact: Available from American Health Assistance Foundation. 15825 Shady Grove Road, Suite 140, Rockville, MD 20850. (800) 437-2423, (301) 948-3244; FAX: (301) 2589454. Internet: http://www.ahaf.org. PRICE: Free. Summary: This annual report of the American Health Assistance Foundation (AHAF) provides 1999 details about Alzheimer's disease research, macular degeneration research, national glaucoma research, National Heart Foundation research, the Alzheimer's Family Relief Program, public education, AHAF development, financial statements, and the board of directors. Each of the sections on research presents information regarding grants awarded in recent fiscal years.

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “macular degeneration” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category.

15 16

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH).

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Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 6430 53 157 3 6 6649

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “macular degeneration” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

17

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

18

The HSTAT URL is http://hstat.nlm.nih.gov/.

19

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 20 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 21

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on macular degeneration can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to macular degeneration. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to macular degeneration. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “macular degeneration”:

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•

Guides on macular degeneration Macular Degeneration http://www.nlm.nih.gov/medlineplus/maculardegeneration.html

•

Other guides Connective Tissue Disorders http://www.nlm.nih.gov/medlineplus/connectivetissuedisorders.html Diabetic Eye Problems http://www.nlm.nih.gov/medlineplus/diabeticeyeproblems.html Eye Diseases http://www.nlm.nih.gov/medlineplus/eyediseases.html Retinal Disorders http://www.nlm.nih.gov/medlineplus/retinaldisorders.html Vision Disorders & Blindness http://www.nlm.nih.gov/medlineplus/visiondisordersblindness.html

Within the health topic page dedicated to macular degeneration, the following was listed: •

General/Overviews Macular Degeneration http://www.nlm.nih.gov/medlineplus/tutorials/maculardegenerationloader.html What Is Macular Degeneration? Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=DS00284

•

Diagnosis/Symptoms Age-Related Macular Degeneration Test Source: Prevent Blindness America http://www.preventblindness.org/eye_tests/amd_test.html

•

Treatment Current Treatments Source: Macular Degeneration Partnership http://amd.convio.net/site/PageServer?pagename=Current_Treatments

•

Nutrition MDP Vitamin Survey Source: Macular Degeneration Partnership http://amd.convio.net/site/FrameSet?style=User&url=http%253A//209.209.54.83 /vitamintool/index.cfm Nutrition's Role Source: Macular Degeneration Partnership http://amd.convio.net/site/PageServer?pagename=Nutrition

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•

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Coping Low Vision Aids Source: Macular Degeneration Partnership http://amd.convio.net/site/PageServer?pagename=Low_Vision_Aids

•

Children Stargardt Disease Source: Foundation Fighting Blindness http://www.blindness.org/visiondisorders/causes.asp?type=5 Stargardt's Disease Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01421

•

From the National Institutes of Health Age-Related Macular Degeneration: What You Should Know Source: National Eye Institute http://www.nei.nih.gov/health/maculardegen/armd_facts.htm Results of the Age-Related Eye Disease Study Source: National Eye Institute http://www.nei.nih.gov/amd/summary.htm

•

Latest News Vitamins Combat Age-Related Blindness Source: 11/10/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14601 .html

•

Organizations American Optometric Association http://www.aoa.org/ Macular Degeneration Partnership http://amd.convio.net/site/PageServer National Eye Institute http://www.nei.nih.gov/

•

Pictures/Diagrams Diagram of the Eye Source: National Eye Institute http://www.nei.nih.gov/health/eyediagram/index.htm

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•

Prevention/Screening How Often to Have an Eye Exam Source: American Academy of Ophthalmology http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZAKCLP3SC& sub_cat=113 What Can I Do About It? Source: Macular Degeneration Partnership http://amd.convio.net/site/PageServer?pagename=What_Can_I_Do

•

Research Lutein and Eye Disease Prevention Source: National Eye Institute http://www.nei.nih.gov/news/statements/lutein.htm Macular Degeneration Treatment Also Effective for Treating Ocular Fungus Disease (Histoplasmosis) Source: American Academy of Ophthalmology http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ8WQ30U4D &sub_cat=2 Research and Experimental Treatments Source: Macular Degeneration Partnership http://amd.convio.net/site/PageServer?pagename=Research There Is Hope for Those with Age-Related Macular Degeneration Source: American Academy of Ophthalmology http://www.medem.com/medlb/article_detaillb.cfm?article_ID=ZZZ74AW55CD &sub_cat=2

•

Statistics Vision Problems in the U.S. Source: National Eye Institute http://www.nei.nih.gov/eyedata/pdf/VPUS.pdf

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on macular degeneration. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search

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options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Macular Degeneration: Healthy Eyes Mean a Better Life Source: St. Louis, MO: American Optometric Association. 1991. 2 p. Contact: Available from American Optometric Association. Order Department, 243 North Lindbergh Boulevard, St. Louis, MO 63141. (314) 991-4100. PRICE: Single copy free (bulk prices available). Order Number FS8. Summary: This patient education fact sheet provides information about macular degeneration. This disorder results from changes to the macula, a portion of the retina that is responsible for clear, sharp central vision. The fact sheet notes causes for macular degeneration, the typical symptoms noted as the condition develops, and some of the treatments and low vision aids available to deal with macular degeneration. An early detection chart, used for self-screening, is included on the verso of the fact sheet. The National Guideline Clearinghouse™

The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “macular degeneration” (or synonyms). The following was recently posted: •

Age-related macular degeneration Source: American Academy of Ophthalmology - Medical Specialty Society; 1998 September (updated 2001 Oct); 33 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3088&nbr=2314&a mp;string=macular+AND+degeneration

•

Care of the patient with age-related macular degeneration Source: American Optometric Association - Professional Association; 1994 (reviewed 1999); 47 pages http://www.guideline.gov/summary/summary.aspx?doc_id=1989&nbr=1215&a mp;string=macular+AND+degeneration Healthfinder™

Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Age-Related Macular Degeneration: Information for Patients Summary: This pamphlet is designed to help people with age-related macular degeneration better understand the disease. Source: National Eye Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=689

224 Macular Degeneration

•

AMD Newsletter Summary: A monthly online newsletter for persons afflicted with age-related macular degeneration and their families. Source: Macular Degeneration Partnership http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4755

•

Are You at Risk for Age-Related Macular Degeneration? Summary: AMD is a common eye disease associated with aging that gradually destroys sharp, central vision. Source: National Eye Institute, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=695

•

Eye Disease Information and Resources Summary: On these pages you will find information about several eye diseases, along with animated depictions of the progression of age-related macular degeneration, cataracts, diabetic retinopathy, dry eye, Source: Schepens Eye Research Institute http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7737

•

Macular Degeneration Help Center Summary: Links to web sites and resources on health, aging, and low vision, along with information, tools and resources for AMD(age-related macular degeneration) patients, their families and older adults. Source: Macular Degeneration Partnership http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=4600

•

Macular Degeneration Research Summary: This document is about the American Health Assistance Foundation's Macular Degeneration Research program, which was established to fund research on and educate the public about macular degeneration. Source: American Health Assistance Foundation http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6684

•

MD Support Summary: This site provides information and support for people dealing with macular degeneration and similar diseases of the retina which may lead to central vision loss. Source: Nonprofit/Professional Entity--Follow the Resource URL for More Information http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6686

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to macular degeneration. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Macular Degeneration The following is a list of associations that provide information on and resources relating to macular degeneration: •

Macular Degeneration International Telephone: (520) 797-2525 Toll-free: ( 80) 683-5555 Fax: (520) 797-8018 Email: [email protected] Web Site: http://www.maculardegeneration.org Background: Macular Degeneration International is a national not-for-profit self-help service organization that was established in 1993. The mission of the organization is to foster scientific research into the nature of the Juvenile Macular Dystrophies and agerelated macular degeneration. The organization also provides educational and support programs to help affected individuals cope with their vision related problems. Macular Degeneration International maintains a database, publishes a quarterly newsletter, hosts conferences, and makes referrals to physicians who are familial with macular dystrophies. Brochures and reports are also available from the organization. Relevant area(s) of interest: Macular Degeneration

226 Macular Degeneration

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to macular degeneration. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with macular degeneration. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about macular degeneration. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “macular degeneration” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “macular degeneration”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “macular degeneration” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “macular degeneration” (or a synonym) into the search box, and click “Submit Query.”

229

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

230 Macular Degeneration

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

232 Macular Degeneration

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

234 Macular Degeneration

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

235

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on macular degeneration: •

Basic Guidelines for Macular Degeneration Macular degeneration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001000.htm

•

Diagnostics and Tests for Macular Degeneration Angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003327.htm Fluorescein angiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003846.htm Refraction test Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003844.htm Retinal photography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003846.htm

236 Macular Degeneration

Slit lamp examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003880.htm Visual acuity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003396.htm Visual field Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003879.htm •

Nutrition for Macular Degeneration Zinc in diet Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002416.htm

•

Surgery and Procedures for Macular Degeneration Laser surgery Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002958.htm

•

Background Topics for Macular Degeneration Central Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm Choroid Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002318.htm Cigarette smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Laser therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001913.htm Macula Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002252.htm Peripheral Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002273.htm Retina Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002291.htm Smoking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002032.htm

Online Glossaries 237

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

239

MACULAR DEGENERATION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abducens: A striated, extrinsic muscle of the eyeball that originates from the annulus of Zinn. [NIH] Abducens Nerve: The 6th cranial nerve. The abducens nerve originates in the abducens nucleus of the pons and sends motor fibers to the lateral rectus muscles of the eye. Damage to the nerve or its nucleus disrupts horizontal eye movement control. [NIH] Abducens Nerve Diseases: Diseases of the sixth cranial (abducens) nerve or its nucleus in the pons. The nerve may be injured along its course in the pons, intracranially as it travels along the base of the brain, in the cavernous sinus, or at the level of superior orbital fissure or orbit. Dysfunction of the nerve causes lateral rectus muscle weakness, resulting in horizontal diplopia that is maximal when the affected eye is abducted and esotropia. Common conditions associated with nerve injury include intracranial hypertension; craniocerebral trauma; ischemia; and infratentorial neoplasms. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablate: In surgery, is to remove. [NIH] Ablation: The removal of an organ by surgery. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Accommodation: Adjustment, especially that of the eye for various distances. [EU] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acne: A disorder of the skin marked by inflammation of oil glands and hair glands. [NIH] Acne Vulgaris: A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH]

240 Macular Degeneration

Acuity: Clarity or clearness, especially of the vision. [EU] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adult-Onset Diabetes: Former term for noninsulin-dependent or type II diabetes. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association

Dictionary 241

constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allergic Rhinitis: Inflammation of the nasal mucous membrane associated with hay fever; fits may be provoked by substances in the working environment. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH]

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Alveolar Process: The thickest and spongiest part of the maxilla and mandible hollowed out into deep cavities for the teeth. [NIH] Amaurosis: Partial or total blindness from any cause. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Aminolevulinic Acid: A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local

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inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Angiogenesis Factor: Substance causing proliferation of new blood vessels. It is found in tissues with high metabolic requirements, such as the retina, and in certain cancers. The factor is also released by hypoxic macrophages at the edges or outer surfaces of wounds and initiates revascularization in wound healing. [NIH] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiogram: An x-ray of blood vessels; the person receives an injection of dye to outline the vessels on the x-ray. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioid Streaks: Small breaks in the elastin-filled tissue of the retina. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Antiangiogenesis: Prevention of the growth of new blood vessels. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the

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lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antiemetics: Drugs used to prevent nausea or vomiting. Antiemetics act by a wide range of mechanisms. Some act on the medullary contol centers (the vomiting center and the chemoreceptive trigger zone) while others affect the peripheral receptors. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial

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infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Apolipoproteins: The protein components of lipoproteins which remain after the lipids to which the proteins are bound have been removed. They play an important role in lipid transport and metabolism. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Aqueous humor: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in

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the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Articular: Of or pertaining to a joint. [EU] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astigmatism: A condition in which the surface of the cornea is not spherical; causes a blurred image to be received at the retina. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asynchronous: Pacing mode where only one timing interval exists, that between the stimuli. While the duration of this interval may be varied, it is not modified by any sensed event once set. As no sensing occurs, the upper and lower rate intervals are the same as the pacema. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial

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impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autosuggestion: Suggestion coming from the subject himself. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other

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parts of the body. [NIH] Benzyl Alcohol: A colorless liquid with a sharp burning taste and slight odor. It is used as a local anesthetic and to reduce pain associated with lidocaine injection. Also, it is used in the manufacture of other benzyl compounds, as a pharmaceutic aid, and in perfumery and flavoring. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta-Galactosidase: A group of enzymes that catalyzes the hydrolysis of terminal, nonreducing beta-D-galactose residues in beta-galactosides. Deficiency of beta-Galactosidase A1 may cause gangliodisosis GM1. EC 3.2.1.23. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Factors: Compounds made by living organisms that contribute to or influence a phenomenon or process. They have biological or physiological activities. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH]

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Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Retinal Barrier: Specialized nonfenestrated tightly-joined endothelial cells that form a transport barrier for certain substances between the retinal capillaries and the retinal tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Mass Index: One of the anthropometric measures of body mass; it has the highest correlation with skinfold thickness or body density. [NIH] Bolus: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus infusion. [NIH] Bolus infusion: A single dose of drug usually injected into a blood vessel over a short period of time. Also called bolus. [NIH] Bolus injection: The injection of a drug (or drugs) in a high quantity (called a bolus) at once, the opposite of gradual administration (as in intravenous infusion). [EU] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Resorption: Bone loss due to osteoclastic activity. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH]

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Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Broadband: A wide frequency range. Sound whose energy is distributed over a broad range of frequency (generally, more than one octave). [NIH] Budesonide: A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs.

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[NIH]

Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cavernous Sinus: An irregularly shaped venous space in the dura mater at either side of the sphenoid bone. [NIH] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called

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nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Count: A count of the number of cells of a specific kind, usually measured per unit volume of sample. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebral: Of or pertaining of the cerebrum or the brain. [EU]

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Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chloride Channels: Cell membrane glycoproteins selective for chloride ions. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis. [NIH] Choriocapillaris: A layer of the choroid between the lamina vitrea and Sattler's layer, consisting of a network of capillaries which supplies the outer 5 layers of the retina; the network is densest at the macula. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroidal Neovascularization: A pathological process consisting of the formation of new blood vessels in the choroid. [NIH] Choroiditis: Inflammation of the choroid. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chylomicrons: A class of lipoproteins that carry dietary cholesterol and triglycerides from the small intestines to the tissues. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [NIH] Ciliary Body: A ring of tissue extending from the scleral spur to the ora serrata of the retina.

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It consists of the uveal portion and the epithelial portion. The ciliary muscle is in the uveal portion and the ciliary processes are in the epithelial portion. [NIH] Ciliary Neurotrophic Factor: A neurotrophic factor that promotes the survival of various neuronal cell types and may play an important role in the injury response in the nervous system. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by

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physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Color blindness: A form of defective color vision requiring only two primary colors, mixed in various proportions, to match all other colors. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials

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including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complement Activation: The sequential activation of serum components C1 through C9, initiated by an erythrocyte-antibody complex or by microbial polysaccharides and properdin, and producing an inflammatory response. [NIH] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Cone cells: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH]

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Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Ulcer: Loss of epithelial tissue from the surface of the cornea due to progressive erosion and necrosis of the tissue; usually caused by bacterial, fungal, or viral infection. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Luteum: The yellow glandular mass formed in the ovary by an ovarian follicle that

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has ruptured and discharged its ovum. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crowding: Behavior with respect to an excessive number of individuals, human or animal, in relation to available space. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]

Cystoid: Like a bladder or a cyst. [NIH]

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Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxins: Substances elaborated by microorganisms, plants or animals that are specifically toxic to individual cells; they may be involved in immunity or may be contained in venoms. [NIH]

Dairy Products: Raw and processed or manufactured milk and milk-derived products. These are usually from cows (bovine) but are also from goats, sheep, reindeer, and water buffalo. [NIH] Dark Adaptation: Adjustment of the eyes under conditions of low light. The sensitivity of the eye to light is increased during dark adaptation. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delusions: A false belief regarding the self or persons or objects outside the self that persists

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despite the facts, and is not considered tenable by one's associates. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Depth Perception: Perception of three-dimensionality. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Diplopia: A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diurnal: Occurring during the day. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and

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for hiccup. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drusen: Tiny yellow or white deposits in the retina or optic nerve head. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH]

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Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Electroretinogram: The electrical effect recorded from the surface of the eyeball and originated by a pulse of light. [NIH] Electroretinography: Recording of electric potentials in the retina after stimulation by light. [NIH]

Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU]

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Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endophthalmitis: Suppurative inflammation of the tissues of the internal structures of the eye; not all layers of the uvea are affected. Fungi, necrosis of intraocular tumors, and retained intraocular foreign bodies often cause a purulent endophthalmitis. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health.

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[NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epiretinal Membrane: Membrane viruses are thought to acquire their envelopes by budding through modified portions of the host cell membrane. [NIH] Episcleritis: Inflammation of the episclera and/or the outer layers of the sclera itself. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epoprostenol: A prostaglandin that is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. It is a potent inhibitor of platelet aggregation. The sodium salt has been also used to treat primary pulmonary hypertension. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Estrogen: One of the two female sex hormones. [NIH] Ethanolamine: A viscous, hygroscopic amino alcohol with an ammoniacal odor. It is widely distributed in biological tissue and is a component of lecithin. It is used as a surfactant, fluorimetric reagent, and to remove CO2 and H2S from natural gas and other gases. [NIH]

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Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excimer laser: An ultraviolet laser used in refractive surgery to remove corneal tissue. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation,

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visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibrinolytic: Pertaining to, characterized by, or causing the dissolution of fibrin by enzymatic action [EU] Fibrinolytic Agents: Fibrinolysin or agents that convert plasminogen to fibrinolysin (plasmin). [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibromuscular Dysplasia: An idiopathic, segmental, nonatheromatous disease of the musculature of arterial walls, leading to stenosis of small and medium-sized arteries. Most commonly affected are the renal arteries; involvement of the axillary, iliac, basilar, carotid, hepatic and intracranial arteries have been reported. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but

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if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Fluid Therapy: Therapy whose basic objective is to restore the volume and composition of the body fluids to normal with respect to water-electrolyte balance. Fluids may be administered intravenously, orally, by intermittent gavage, or by hypodermoclysis. [NIH] Fluorescein Angiography: Visualization of a vascular system after intravenous injection of a fluorescein solution. The images may be photographed or televised. It is used especially in studying the retinal and uveal vasculature. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Foetoplacental: Pertaining to the fetus and placenta. [EU] Forearm: The part between the elbow and the wrist. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Galactosides: Glycosides formed by the reaction of the hydroxyl group on the anomeric carbon atom of galactose with an alcohol to form an acetal. They include both alpha- and beta-galactosides. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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Gastrointestinal: Refers to the stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gelatinase A: A secreted endopeptidase homologous with interstitial collagenase, but which possesses an additional fibronectin-like domain. EC 3.4.24.24. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Giant Cells: Multinucleated masses produced by the fusion of many cells; often associated with viral infections. In AIDS, they are induced when the envelope glycoprotein of the HIV virus binds to the CD4 antigen of uninfected neighboring T4 cells. The resulting syncytium leads to cell death and thus may account for the cytopathic effect of the virus. [NIH] Gigantism: The condition of abnormal overgrowth or excessive size of the whole body or any of its parts. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

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Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Gluconeogenesis: The process by which glucose is formed from a non-carbohydrate source. [NIH]

Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycogen: A sugar stored in the liver and muscles. It releases glucose into the blood when cells need it for energy. Glycogen is the chief source of stored fuel in the body. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Goats: Any of numerous agile, hollow-horned ruminants of the genus Capra, closely related to the sheep. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grading: A system for classifying cancer cells in terms of how abnormal they appear when

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examined under a microscope. The objective of a grading system is to provide information about the probable growth rate of the tumor and its tendency to spread. The systems used to grade tumors vary with each type of cancer. Grading plays a role in treatment decisions. [NIH]

Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Health Education: Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematoporphyrins: Iron-free derivatives of heme with 4 methyl groups, 2 hydroxyethyl groups and 2 propionic acid groups attached to the pyrrole rings. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH]

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Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobin A: Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterodimer: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Antagonists: Chemical substances which inhibit the function of the endocrine glands, the biosynthesis of their secreted hormones, or the action of hormones upon their

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specific sites. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Human growth hormone: A protein hormone, secreted by the anterior lobe of the pituitary, which promotes growth of the whole body by stimulating protein synthesis. The human gene has already been cloned and successfully expressed in bacteria. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipoproteinemia: Metabolic disease characterized by elevated plasma cholesterol and/or triglyceride levels. The inherited form is attributed to a single gene mechanism. [NIH] Hyperopia: Farsightedness; ability to see distant objects more clearly than close objects; may be corrected with glasses or contact lenses. [NIH] Hyperpigmentation: Excessive pigmentation of the skin, usually as a result of increased melanization of the epidermis rather than as a result of an increased number of melanocytes. Etiology is varied and the condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH]

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Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Iatrogenic: Resulting from the activity of physicians. Originally applied to disorders induced in the patient by autosuggestion based on the physician's examination, manner, or discussion, the term is now applied to any adverse condition in a patient occurring as the result of treatment by a physician or surgeon, especially to infections acquired by the patient during the course of treatment. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Ileum: The lower end of the small intestine. [NIH] Iloprost: An eicosanoid, derived from the cyclooxygenase pathway of arachidonic acid metabolism. It is a stable and synthetic analog of epoprostenol, but with a longer half-life than the parent compound. Its actions are similar to prostacyclin. Iloprost produces vasodilation and inhibits platelet aggregation. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA

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synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called

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intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Instillation: . [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Interstitial Collagenase: A member of the metalloproteinase family of enzymes that is principally responsible for cleaving fibrillar collagen. It can degrade interstitial collagens, types I, II and III. EC 3.4.24.7. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [NIH]

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Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritants: Drugs that act locally on cutaneous or mucosal surfaces to produce inflammation; those that cause redness due to hyperemia are rubefacients; those that raise blisters are vesicants and those that penetrate sebaceous glands and cause abscesses are pustulants; tear gases and mustard gases are also irritants. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isotretinoin: A topical dermatologic agent that is used in the treatment of acne vulgaris and several other skin diseases. The drug has teratogenic and other adverse effects. [NIH] Kallikreins: Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increases vascular permeability and affects smooth muscle. They act as infertility agents in men. Three forms are recognized, plasma kallikrein (EC 3.4.21.34), tissue kallikrein (EC 3.4.21.35), and prostate-specific antigen (EC 3.4.21.77). [NIH]

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Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Krypton: A noble gas that is found in the atmosphere. It has the atomic symbol Kr, atomic number 36, atomic weight 83.80, and has been used in electric bulbs. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laser Surgery: The use of a laser either to vaporize surface lesions or to make bloodless cuts in tissue. It does not include the coagulation of tissue by laser. [NIH] Laser therapy: The use of an intensely powerful beam of light to kill cancer cells. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Legal blindness: In the U.S., (1) visual acuity of 20/200 or worse in the better eye with corrective lenses (20/200 means that a person must be at 20 feet from an eye chart to see what a person with normal vision can see at 200 feet) or (2) visual field restricted to 20 d [NIH]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal

Dictionary 279

tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Liposomal: A drug preparation that contains the active drug in very tiny fat particles. This fat-encapsulated drug is absorbed better, and its distribution to the tumor site is improved. [NIH]

Liposome: A spherical particle in an aqueous medium, formed by a lipid bilayer enclosing

280 Macular Degeneration

an aqueous compartment. [EU] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobsters: Large marine decapod crustaceans of the family Homaridae, commonly used for food. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low vision: Visual loss that cannot be corrected with eyeglasses or contact lenses and interferes with daily living activities. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lumen: The cavity or channel within a tube or tubular organ. [EU] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen,

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thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Activation: The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]

Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU]

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Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Membrane Potentials: Ratio of inside versus outside concentration of potassium, sodium, chloride and other ions in diffusible tissues or cells. Also called transmembrane and resting potentials, they are measured by recording electrophysiologic responses in voltagedependent ionic channels of (e.g.) nerve, muscle and blood cells as well as artificial membranes. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastasize: To spread from one part of the body to another. When cancer cells metastasize and form secondary tumors, the cells in the metastatic tumor are like those in the original (primary) tumor. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of

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the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microgram: A unit of mass (weight) of the metric system, being one-millionth of a gram (106 gm.) or one one-thousandth of a milligram (10-3 mg.). [EU] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Midaxillary line: An imaginary vertical line that passes midway between the anterior and posterior axillary (armpit) folds. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Millimeter: A measure of length. A millimeter is approximately 26-times smaller than an inch. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Minority Groups: A subgroup having special characteristics within a larger group, often bound together by special ties which distinguish it from the larger group. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired

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from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary

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arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoglobin: A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic axis are brought to a focus in front of the retina, as a result of the eyeball being too long from front to back (axial m.) or of an increased strength in refractive power of the media of the eye (index m.). Called also nearsightedness, because the near point is less distant than it is in emmetropia with an equal amplitude of accommodation. [EU] N-acetyl: Analgesic agent. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Nearsightedness: The common term for myopia. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neomycin: Antibiotic complex produced by Streptomyces fradiae. It is composed of neomycins A, B, and C. It acts by inhibiting translation during protein synthesis. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH]

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Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH]

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Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nutritional Support: The administration of nutrients for assimilation and utilization by a patient by means other than normal eating. It does not include fluid therapy which normalizes body fluids to restore water-electrolyte balance. [NIH] Nystagmus: Rhythmical oscillation of the eyeballs, either pendular or jerky. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Ocular Hypertension: A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oculomotor Nerve: The 3d cranial nerve. The oculomotor nerve sends motor fibers to the levator muscles of the eyelid and to the superior rectus, inferior rectus, and inferior oblique muscles of the eye. It also sends parasympathetic efferents (via the ciliary ganglion) to the muscles controlling pupillary constriction and accommodation. The motor fibers originate in the oculomotor nuclei of the midbrain. [NIH] Oestrogen: A generic term for oestrus-producing steroid compounds; the female sex hormones. In humans, oestrogen is formed in the ovary, possibly the adrenal cortex, the testis, and the foetoplacental unit; it has various functions in both sexes. It is responsible for the development of the female secondary sex characteristics, and during the menstrual cycle it acts on the female genitalia to produce an environment suitable for the fertilization, implantation, and nutrition of the early embryo. Oestrogen is used in oral contraceptives and as a palliative in cancer of the breast after menopause and cancer of the prostate; other uses include the relief of the discomforts of menopause, inhibition of lactation, and treatment of osteoporosis, threatened abortion, and various functional ovarian disorders. [EU]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Ophthalmoscope: A lighted instrument used to examine the inside of the eye, including the

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retina and the optic nerve. [NIH] Ophthalmoscopy: Examination of the interior of the eye with an ophthalmoscope. [NIH] Opsin: A visual pigment protein found in the retinal rods. It combines with retinaldehyde to form rhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Disk: The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. [NIH] Optic nerve head: The circular area (disc) where the optic nerve connects to the retina. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of

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an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural

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and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pericytes: Smooth muscle cell that wraps around normal blood vessels. [NIH] Perimetry: Determination of the extent of the visual field for various types and intensities of stimuli. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH]

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Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH] Photodynamic therapy: Treatment with drugs that become active when exposed to light. These drugs kill cancer cells. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Photosensitizer: A drug used in photodynamic therapy. When absorbed by cancer cells and exposed to light, the drug becomes active and kills the cancer cells. [NIH] Photosensitizing Agents: Drugs that are pharmacologically inactive but when exposed to ultraviolet radiation or sunlight are converted to their active metabolite to produce a beneficial reaction affecting the diseased tissue. These compounds can be administered topically or systemically and have been used therapeutically to treat psoriasis and various types of neoplasms. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their

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cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pigmentation: Coloration or discoloration of a part by a pigment. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Kallikrein: A peptidohydrolytic enzyme that is formed from prekallikrein by factor XIIA. It activates factor XII, factor VII, and plasminogen. It is selective for both arginine and to a lesser extent lysinebonds. EC 3.4.21.34. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness,

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aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Polychromatic: Erythrocyte that, on staining, shows various shades of blue combined with tinges of pink. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] Porfimer sodium: An anticancer drug that is also used in cancer prevention. It belongs to the family of drugs called photosensitizing agents. [NIH] Porphyrins: A group of compounds containing the porphin structure, four pyrrole rings connected by methine bridges in a cyclic configuration to which a variety of side chains are attached. The nature of the side chain is indicated by a prefix, as uroporphyrin, hematoporphyrin, etc. The porphyrins, in combination with iron, form the heme component in biologically significant compounds such as hemoglobin and myoglobin. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH]

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Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Presbyopia: The normal decreasing elasticity of the crystalline lens that leads to loss of accommodation. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Primary tumor: The original tumor. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is

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PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Prostate-Specific Antigen: Kallikrein-like serine proteinase produced by epithelial cells of both benign and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer. EC 3.4.21.77. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteoglycans: Glycoproteins which have a very high polysaccharide content. [NIH]

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Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudoxanthoma: A rare disease of the skin characterized by the appearance of elevated yellowish papules or plaques, particularly on the neck, chest an abdomen and infrequently on the eyelids. [NIH] Pseudoxanthoma Elasticum: A rare, progressive inherited disorder resulting from extensive basophilic degeneration of elastic tissue, usually presenting after puberty and involving the skin, eye, and cardiovascular system. Characteristic manifestations are small, circumscribed yellowish patches at sites of considerable movement of the skin, angioid streaks in the retina, and a tendency towards hemorrhage and arterial insufficiency. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of

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literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulmonary Fibrosis: Chronic inflammation and progressive fibrosis of the pulmonary alveolar walls, with steadily progressive dyspnea, resulting finally in death from oxygen lack or right heart failure. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Purulent: Consisting of or containing pus; associated with the formation of or caused by pus. [EU] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH]

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Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractive Errors: Deviations from the average or standard indices of refraction of the eye through its dioptric or refractive apparatus. [NIH] Refractive Power: The ability of an object, such as the eye, to bend light as light passes through it. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of

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treatment. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [NIH]

Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Residual disease: Cancer cells that remain after attempts have been made to remove the cancer. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticulocytes: Immature erythrocytes. In humans, these are erythroid cells that have just undergone extrusion of their cell nucleus. They still contain some organelles that gradually decrease in number as the cells mature. ribosomes are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the endoplasmic reticulum), hence the name reticulocytes. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinae: A congenital notch or cleft of the retina, usually located inferiorly. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour

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vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinal Hemorrhage: Bleeding from the vessels of the retina. [NIH] Retinal Neovascularization: Formation of new blood vessels originating from the retinal veins and extending along the inner (vitreal) surface of the retina. [NIH] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinal Vein: Central retinal vein and its tributaries. It runs a short course within the optic nerve and then leaves and empties into the superior ophthalmic vein or cavernous sinus. [NIH]

Retinal Vein Occlusion: Occlusion of the retinal vein. Those at high risk for this condition include patients with hypertension, diabetes mellitus, arteriosclerosis, and other cardiovascular diseases. [NIH] Retinal Vessels: The vessels which supply and drain the retina. [NIH] Retinaldehyde: A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in "dark" reactions to return to the native transconfiguration. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]

Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH]

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Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retreatment: The therapy of the same disease in a patient, with the same agent or procedure repeated after initial treatment, or with an additional or alternate measure or follow-up. It does not include therapy which requires more than one administration of a therapeutic agent or regimen. Retreatment is often used with reference to a different modality when the original one was inadequate, harmful, or unsuccessful. [NIH] Retrobulbar: Behind the pons. [EU] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rod cells: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Rod Outer Segments: The portion of the retinal rod cell between the inner segment and the pigment epithelium layer of the retina. [NIH] Rose Bengal: A bright bluish pink compound that has been used as a dye, biological stain, and diagnostic aid. [NIH] Rubber: A high-molecular-weight polymeric elastomer derived from the milk juice (latex) of Hevea brasiliensis and other trees. It is a substance that can be stretched at room temperature to atleast twice its original length and after releasing the stress, retractrapidly, and recover its original dimensions fully. Synthetic rubber is made from many different chemicals, including styrene, acrylonitrile, ethylene, propylene, and isoprene. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcoidosis: An idiopathic systemic inflammatory granulomatous disorder comprised of epithelioid and multinucleated giant cells with little necrosis. It usually invades the lungs with fibrosis and may also involve lymph nodes, skin, liver, spleen, eyes, phalangeal bones, and parotid glands. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in

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cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Scleritis: Refers to any inflammation of the sclera including episcleritis, a benign condition affecting only the episclera, which is generally short-lived and easily treated. Classic scleritis, on the other hand, affects deeper tissue and is characterized by higher rates of visual acuity loss and even mortality, particularly in necrotizing form. Its characteristic symptom is severe and general head pain. Scleritis has also been associated with systemic collagen disease. Etiology is unknown but is thought to involve a local immune response. Treatment is difficult and includes administration of anti-inflammatory and immunosuppressive agents such as corticosteroids. Inflammation of the sclera may also be secondary to inflammation of adjacent tissues, such as the conjunctiva. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scotoma: A localized defect in the visual field bordered by an area of normal vision. This occurs with a variety of eye diseases (e.g., retinal diseases and glaucoma), optic nerve diseases, and other conditions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH]

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Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sharpness: The apparent blurring of the border between two adjacent areas of a radiograph having different optical densities. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological

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activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters

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distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrometer: An apparatus for determining spectra; measures quantities such as wavelengths and relative amplitudes of components. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereoscopic: Accurate depth perception in the presence of binocular single vision, due to the slight disparity in the two retinal images of the same object. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulants: Any drug or agent which causes stimulation. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Strabismus: Deviation of the eye which the patient cannot overcome. The visual axes assume a position relative to each other different from that required by the physiological conditions. The various forms of strabismus are spoken of as tropias, their direction being

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indicated by the appropriate prefix, as cyclo tropia, esotropia, exotropia, hypertropia, and hypotropia. Called also cast, heterotropia, manifest deviation, and squint. [EU] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Styrene: A colorless, toxic liquid with a strong aromatic odor. It is used to make rubbers, polymers and copolymers, and polystyrene plastics. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subconjunctival: Situated or occurring beneath the conjunctiva. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic

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nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tamponade: The inserting of a tampon; a dressing is inserted firmly into a wound or body cavity, as the nose, uterus or vagina, principally for stopping hemorrhage. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Tear Gases: Gases that irritate the eyes, throat, or skin. Severe lacrimation develops upon irritation of the eyes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Teletherapy: Radiotherapy with a souce-skin distance that is large compared to the dimensions of the irradiated tissue being treated. [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss,

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movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombolytic Therapy: Use of infusions of fibrinolytic agents to destroy or dissolve thrombi in blood vessels or bypass grafts. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thymus: An organ that is part of the lymphatic system, in which T lymphocytes grow and multiply. The thymus is in the chest behind the breastbone. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH]

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Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH] Tomograph: An X-ray apparatus; an instrument that produces a relatively sharp image of a thin layer of the object, all other layers being blurred by predetermined relative motion of the roentgen tube, film, and subject. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] Tonometer: For testing the intra-ocular tension. [NIH] Tooth Loss: The failure to retain teeth as a result of disease or injury. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transducin: A heterotrimeric GTP-binding protein that mediates the light activation signal from photolyzed rhodopsin to cyclic GMP phosphodiesterase and is pivotal in the visual excitation process. Activation of rhodopsin on the outer membrane of rod and cone cells causes GTP to bind to transducin followed by dissociation of the alpha subunit-GTP complex from the beta/gamma subunits of transducin. The alpha subunit-GTP complex activates the cyclic GMP phosphodiesterase which catalyzes the hydrolysis of cyclic GMP to 5'-GMP. This leads to closure of the sodium and calcium channels and therefore hyperpolarization of the rod cells. EC 3.6.1.-. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH]

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Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Transversion: A base-pair substitution mutation in which a purine-pyrimidine pair is replaced by the equivalent pyrimidine-purine pair, i. e. A-T becomes T-A. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triamcinolone Acetonide: An esterified form of triamcinolone. It is an anti-inflammatory glucocorticoid used topically in the treatment of various skin disorders. Intralesional, intramuscular, and intra-articular injections are also administered under certain conditions. [NIH]

Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trochlear Nerve: The 4th cranial nerve. The trochlear nerve carries the motor innervation of the superior oblique muscles of the eye. [NIH] Trochlear Nerve Diseases: Diseases of the fourth cranial (trochlear) nerve or its nucleus in the midbrain. The nerve crosses as it exits the midbrain dorsally and may be injured along its course through the intracranial space, cavernous sinus, superior orbital fissure, or orbit. Clinical manifestations include weakness of the superior oblique muscle which causes vertical diplopia that is maximal when the affected eye is adducted and directed inferiorly. Head tilt may be seen as a compensatory mechanism for diplopia and rotation of the visual axis. Common etiologies include craniocerebral trauma and infratentorial neoplasms. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumor marker: A substance sometimes found in an increased amount in the blood, other body fluids, or tissues and which may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (prostate cancer). Also called biomarker. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH]

Dictionary 311

Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Plasminogen Activator: A proteolytic enzyme that converts plasminogen to plasmin where the preferential cleavage is between arginine and valine. It was isolated originally from human urine, but is found in most tissues of most vertebrates. EC 3.4.21.73. [NIH]

Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Uvea: The middle coat of the eyeball, consisting of the choroid in the back of the eye and the ciliary body and iris in the front of the eye. [NIH] Uveitis: An inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (the sclera and cornea, and the retina). [EU] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular endothelial growth factor: VEGF. A substance made by cells that stimulates new blood vessel formation. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]

312 Macular Degeneration

Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Visual Acuity: Acuteness or clearness of vision, especially of form vision, which is dependent mainly on the sharpness of the retinal focus. [NIH] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral

Dictionary 313

vision. [NIH] Visual Perception: The selecting and organizing of visual stimuli based on the individual's past experience. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Waist circumference: To define the level at which the waist circumference is measured, a bony landmark is first located and marked. The subject stands, and the technician, positioned to the right of the subject, palpates the upper hip bone to locate the right ileum. Just above the uppermost lateral border of the right ileum, a horizontal mark is drawn and then crossed with a vertical mark on the midaxillary line. The measuring tape is then placed around the trunk, at the level of the mark on the right side, making sure that it is on a level horizontal plane on all sides. The tape is then tightened slightly without compressing the skin and underlying subcutaneous tissues. The measure is recorded in centimeters to the nearest millimeter. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] Weight-Bearing: The physical state of supporting an applied load. This often refers to the weight-bearing bones or joints that support the body's weight, especially those in the spine, hip, knee, and foot. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthophyll: A carotenoid alcohol widespread in nature. It is present in egg yolk, algae, and petals of yellow flowers, among other sources. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment

314 Macular Degeneration

is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

315

INDEX 3 3-dimensional, 53, 239, 295 A Abdomen, 134, 239, 249, 280, 296, 305, 308 Abducens, 239, 261 Abducens Nerve, 239, 261 Abducens Nerve Diseases, 239, 261 Aberrant, 17, 20, 44, 50, 59, 239 Ablate, 157, 167, 191, 239, 263 Ablation, 167, 239 Acceptor, 239, 279, 289 Accommodation, 239, 285, 287, 294 ACE, 74, 239 Acetylcysteine, 239 Acne, 60, 101, 239, 277 Acne Vulgaris, 239, 277 Acrylonitrile, 239, 301 Actin, 18, 239 Activities of Daily Living, 25, 239 Acuity, 10, 44, 68, 72, 75, 96, 127, 129, 130, 133, 134, 135, 139, 141, 143, 151, 153, 161, 162, 179, 181, 185, 187, 193, 236, 240, 257, 278, 288, 302, 312 Acyl, 155, 240 Adaptability, 240, 252 Adaptation, 50, 58, 68, 240, 259, 286 Adenine, 240 Adenosine, 192, 240, 291 Adenosine Triphosphate, 192, 240, 291 Adenovirus, 33, 73, 240, 300 Adipocytes, 240, 256, 278 Adjustment, 167, 239, 240, 259 Adrenal Cortex, 240, 241, 258, 287, 294 Adrenal Glands, 240, 242 Adrenergic, 240, 244, 261, 265, 306 Adult-Onset Diabetes, 187, 240 Adverse Effect, 240, 277, 303 Aerobic, 8, 240, 283 Afferent, 240, 278, 288, 291 Affinity, 240, 241, 246, 304 Agar, 241, 292 Age of Onset, 24, 32, 241, 311 Agonist, 43, 157, 241, 261 Albumin, 241, 292 Aldosterone, 182, 241 Alexia, 241, 262 Algorithms, 241, 248 Alkaline, 241, 242, 250

Alleles, 5, 53, 54, 77, 241, 272, 279 Allergen, 241, 260, 303 Allergic Rhinitis, 241, 250 Allogeneic, 241, 271 Allylamine, 241, 242 Alpha Particles, 241, 297 Alternative medicine, 205, 241 Alveolar Process, 242, 299 Amaurosis, 7, 53, 242 Amber, 16, 242 Ameliorated, 157, 242 Ameliorating, 169, 242 Amine, 149, 165, 242 Amino Acid Sequence, 186, 242, 243, 269 Amino Acids, 151, 186, 242, 269, 290, 293, 295, 301, 303, 306, 309 Aminolevulinic Acid, 158, 242 Ammonia, 242 Amyloidosis, 71, 242 Anaesthesia, 242, 275 Anal, 242, 268 Analgesic, 242, 279, 285 Analog, 242, 274 Analogous, 242, 262, 309 Anaphylatoxins, 242, 256 Anatomical, 27, 153, 190, 243, 247, 257, 275, 302 Androgens, 240, 243, 258 Anemia, 158, 243 Anesthesia, 142, 243 Aneurysm, 171, 243, 245, 311 Angiogenesis Factor, 41, 93, 160, 180, 243 Angiogenesis inhibitor, 14, 53, 243, 264 Angiogram, 66, 133, 243 Angiography, 130, 133, 134, 144, 176, 235, 243 Angioid Streaks, 168, 180, 243, 296 Animal model, 12, 14, 27, 29, 31, 33, 34, 37, 48, 53, 56, 152, 160, 171, 243 Anions, 241, 243, 277, 306 Anomalies, 171, 177, 184, 243, 307 Anterior chamber, 41, 243, 277 Antiallergic, 243, 258 Antiangiogenesis, 111, 243 Antiangiogenic, 44, 47, 111, 120, 169, 204, 243 Antibacterial, 243, 305 Antibiotic, 243, 285, 305, 307

316 Macular Degeneration

Antibodies, 12, 83, 162, 171, 174, 185, 191, 243, 244, 272, 274, 281, 284, 292, 297 Anticoagulant, 111, 244, 295, 313 Antiemetics, 244, 261 Antigen, 29, 161, 240, 243, 244, 255, 269, 272, 273, 274, 275, 276, 282, 300, 303 Antigen-Antibody Complex, 244, 255 Anti-inflammatory, 130, 166, 174, 179, 244, 246, 252, 258, 270, 302, 310 Anti-Inflammatory Agents, 166, 244, 246, 252, 258 Antimicrobial, 244, 260 Antineoplastic, 244, 258 Antioxidant, 8, 31, 36, 44, 46, 49, 92, 93, 108, 109, 110, 117, 118, 119, 120, 154, 163, 244, 289 Antipsychotic, 244, 261 Antipsychotic Agents, 244, 261 Antiviral, 239, 245 Aorta, 245, 312 Aortic Aneurysm, 171, 245 Aperture, 26, 28, 245, 297 Aphakia, 245, 300 Apolipoproteins, 245, 279 Aponeurosis, 245, 268 Apoptosis, 5, 9, 29, 30, 34, 47, 51, 180, 188, 245, 251 Applicability, 189, 245 Aqueous, 164, 176, 190, 245, 247, 254, 259, 263, 273, 278, 279 Aqueous fluid, 164, 245 Aqueous humor, 190, 245, 254 Arachidonate 12-Lipoxygenase, 245, 280 Arachidonate 15-Lipoxygenase, 245, 280 Arachidonate Lipoxygenases, 245, 280 Arachidonic Acid, 16, 33, 245, 274, 278, 294 Argon, 134, 139, 141, 143, 246 Arterial, 15, 170, 171, 183, 241, 246, 253, 257, 267, 273, 295, 296, 307 Arteries, 10, 17, 81, 245, 246, 249, 251, 253, 257, 267, 280, 283, 285, 297, 308 Arterioles, 164, 246, 249, 250 Arteriolosclerosis, 246 Arteriosclerosis, 139, 150, 183, 246, 273, 300 Articular, 246, 288, 310 Aspirin, 140, 246 Assay, 5, 9, 11, 14, 48, 54, 246 Astigmatism, 246, 298 Astrocytes, 25, 246 Asynchronous, 39, 246

Ataxia, 105, 246, 308 Atrial, 89, 246, 257, 310, 313 Atrial Fibrillation, 89, 246, 313 Atrioventricular, 247, 257 Atrium, 246, 247, 257, 310, 312 Atrophy, 22, 32, 76, 77, 92, 161, 163, 247, 285 Auditory, 247, 266 Autologous, 11, 34, 59, 63, 247 Autosuggestion, 247, 274 Axillary, 247, 267, 283 Axons, 247, 285, 288, 300 B Bacteria, 8, 28, 240, 243, 244, 247, 258, 263, 264, 266, 267, 271, 272, 273, 283, 292, 305, 309, 311 Bacterial Physiology, 240, 247 Bacteriophage, 247, 292, 309 Basal Ganglia, 35, 244, 246, 247, 268 Basal Ganglia Diseases, 246, 247 Base, 15, 37, 186, 239, 240, 247, 258, 260, 269, 278, 307, 310 Base Sequence, 247, 258, 269 Basement Membrane, 152, 153, 182, 192, 247, 266, 278 Basophils, 247, 271, 278 Benign, 158, 159, 169, 246, 247, 268, 285, 289, 295, 298, 302 Benign tumor, 169, 247 Benzyl Alcohol, 135, 248 Beta carotene, 109, 118, 119, 248 Beta-Galactosidase, 15, 248 Bilateral, 43, 64, 89, 248, 300 Bile, 248, 268, 280, 305, 307 Bile Acids, 248, 305, 307 Bile Ducts, 248 Biliary, 154, 155, 248 Bioavailability, 36, 190, 248 Biochemical, 7, 8, 9, 10, 11, 21, 32, 33, 35, 37, 42, 52, 57, 64, 108, 241, 248, 269, 278 Biological Factors, 56, 248 Biological therapy, 248, 271 Biological Transport, 248, 260 Biomarkers, 37, 248 Biosynthesis, 59, 64, 246, 248, 272, 303 Biotechnology, 59, 60, 108, 158, 198, 205, 215, 248 Bladder, 248, 258, 268, 295, 311 Blastocyst, 248, 292 Blood Coagulation, 249, 250, 308 Blood Glucose, 249, 272, 276

Index 317

Blood pressure, 44, 81, 100, 134, 140, 171, 249, 251, 273, 284, 297, 304 Blood-Retinal Barrier, 18, 51, 159, 249 Blot, 18, 33, 249 Body Fluids, 248, 249, 250, 268, 287, 304, 310 Body Mass Index, 96, 140, 249 Bolus, 157, 249 Bolus infusion, 249 Bolus injection, 157, 249 Bone Marrow, 11, 249, 274, 280, 284, 304, 306 Bone Resorption, 148, 149, 249 Bone scan, 249, 302 Bowel, 242, 249, 261 Bowel Movement, 249, 261 Brachytherapy, 64, 161, 249, 276, 277, 297, 314 Bradykinin, 249, 292 Brain Stem, 249, 261 Branch, 55, 133, 141, 202, 233, 250, 259, 263, 281, 289, 296, 304, 308 Breakdown, 151, 175, 191, 250, 252, 260, 268 Broadband, 167, 250 Budesonide, 55, 250 Bypass, 250, 308 C Calcification, 17, 246, 250 Calcium, 148, 250, 254, 255, 281, 283, 304, 309 Calcium Carbonate, 148, 250 Calcium Channels, 250, 309 Capillary, 14, 152, 156, 166, 170, 172, 182, 192, 249, 250, 312 Capsules, 131, 250, 262, 269 Carbohydrate, 42, 250, 258, 270, 293, 303 Carbon Dioxide, 250, 258, 268, 292, 299 Carcinogenesis, 192, 250 Carcinogenic, 250, 276, 287, 294, 305 Carcinogens, 250, 284, 287, 289 Carcinoma, 14, 250 Cardiac, 41, 89, 241, 246, 251, 257, 263, 265, 279, 285, 305 Cardiovascular, 14, 15, 19, 36, 70, 83, 139, 140, 170, 250, 251, 278, 296, 300 Cardiovascular disease, 14, 15, 19, 70, 83, 139, 140, 170, 251, 300 Cardiovascular System, 251, 296 Carnitine, 154, 155, 251 Carotene, 124, 140, 143, 248, 251, 299

Carotenoids, 10, 69, 97, 108, 109, 111, 122, 125, 144, 168, 193, 248, 251 Carotid Arteries, 10, 251 Carrier Proteins, 251, 292 Case report, 98, 251, 254 Case series, 251, 254 Caspase, 34, 251 Catecholamine, 251, 261 Cations, 251, 277 Caudal, 251, 293 Causal, 251, 272 Cavernous Sinus, 239, 251, 300, 310 Celecoxib, 130, 134, 251 Cell Adhesion, 153, 188, 252, 276 Cell Count, 18, 252 Cell Cycle, 20, 41, 252, 258 Cell Death, 8, 9, 14, 21, 23, 29, 34, 36, 41, 46, 245, 252, 269, 285 Cell Differentiation, 33, 42, 192, 252, 304 Cell Division, 41, 247, 252, 259, 271, 283, 292 Cell membrane, 248, 250, 251, 252, 253, 260, 265, 277, 291, 304 Cell Polarity, 5, 252 Cell proliferation, 40, 51, 169, 192, 246, 252, 300, 304 Cell Respiration, 252, 283, 299 Cell Size, 40, 252 Cell Survival, 51, 56, 182, 252, 271 Cell Transplantation, 11, 76, 252 Cellular metabolism, 155, 252 Cellulose, 252, 292 Central Nervous System, 250, 252, 266, 268, 278, 288, 293 Cerebellar, 246, 252, 298 Cerebral, 246, 247, 249, 252, 265, 266, 287, 297, 307 Cerebrovascular, 139, 247, 251, 253, 308 Ceroid, 253, 279 Character, 253, 259 Chemotactic Factors, 253, 256 Chloride Channels, 49, 60, 253 Chlorophyll, 253, 258 Chloroplasts, 253, 258 Cholesterol, 16, 19, 31, 134, 138, 140, 144, 155, 202, 248, 253, 257, 273, 279, 280, 305 Cholesterol Esters, 253, 279 Choriocapillaris, 18, 28, 66, 109, 119, 156, 161, 167, 185, 253 Chorioretinitis, 253, 300 Choroiditis, 180, 253 Chromatin, 28, 245, 253, 265, 286

318 Macular Degeneration

Chromosomal, 23, 54, 60, 186, 253, 269, 292, 302, 307 Chromosome, 17, 24, 32, 78, 253, 271, 279, 302, 307 Chronic, 68, 160, 163, 164, 170, 183, 184, 239, 253, 255, 261, 275, 280, 296, 297, 306 Chronic Disease, 170, 253, 255 Chylomicrons, 253, 279 Ciliary, 21, 164, 245, 253, 254, 287, 311 Ciliary Arteries, 164, 253 Ciliary Body, 253, 254, 311 Ciliary Neurotrophic Factor, 21, 254 Ciliary processes, 245, 254 Circadian, 40, 50, 254 Circadian Rhythm, 40, 254 Circulatory system, 182, 254 CIS, 7, 53, 254, 269, 299, 300 Citric Acid, 190, 254 Citrus, 254 Clamp, 49, 254 Clear cell carcinoma, 254, 260 Clinical Medicine, 48, 162, 171, 254, 294 Clinical study, 83, 91, 254, 257 Clinical trial, 4, 14, 29, 39, 41, 43, 117, 118, 129, 139, 143, 144, 145, 215, 254, 257, 296, 298 Clone, 7, 14, 52, 254 Cloning, 14, 32, 248, 254 Coagulation, 179, 249, 254, 272, 278, 292, 308, 313 Cochlear, 255, 308, 312 Cochlear Diseases, 255, 308 Coenzyme, 70, 109, 125, 255 Cofactor, 255, 295, 308 Collagen, 170, 247, 255, 266, 269, 276, 281, 293, 294, 302 Collagen disease, 255, 302 Collapse, 250, 255 Color blindness, 178, 255 Combinatorial, 42, 255 Comorbidity, 68, 255 Complement, 6, 60, 189, 242, 255, 256, 269, 276, 292, 303 Complement Activation, 6, 60, 242, 256 Complementary and alternative medicine, 117, 118, 126, 256 Complementary medicine, 118, 256 Computational Biology, 215, 256 Computed tomography, 256, 302 Computerized axial tomography, 256, 302 Concomitant, 8, 256

Cone, 4, 22, 30, 32, 39, 42, 45, 51, 52, 56, 67, 161, 176, 256, 291, 309 Cone cells, 42, 256, 309 Conjugated, 256, 259, 285 Conjunctiva, 178, 253, 256, 302, 306 Connective Tissue, 175, 220, 249, 255, 256, 267, 268, 269, 280, 301 Connective Tissue Cells, 256 Consciousness, 242, 256, 261 Constipation, 195, 244, 257 Constitutional, 257, 300 Constriction, 257, 277, 287, 302, 311 Constriction, Pathologic, 257, 311 Consumption, 204, 257, 260, 299 Contraindications, ii, 257 Contrast Sensitivity, 142, 257, 288 Controlled clinical trial, 96, 139, 257 Controlled study, 92, 257 Cor, 23, 257 Cornea, 26, 30, 130, 178, 181, 190, 193, 243, 245, 246, 257, 302, 306, 311 Corneal Ulcer, 182, 257 Coronary, 139, 154, 251, 257, 283, 284 Coronary heart disease, 154, 251, 257 Coronary Thrombosis, 257, 283, 285 Corpus, 192, 257, 294 Corpus Luteum, 192, 257, 294 Corpuscle, 258, 265 Cortex, 246, 258, 266, 297, 298 Cortical, 258, 266, 307 Corticosteroid, 55, 135, 144, 258 Cranial, 239, 258, 276, 287, 288, 290, 310, 312 Craniocerebral Trauma, 239, 247, 258, 308, 310 Crowding, 47, 258 Cultured cells, 53, 258 Curative, 258, 308 Cutaneous, 17, 258, 277 Cyanobacteria, 10, 258 Cyclic, 31, 258, 291, 293, 295, 302, 309 Cyclin, 22, 258 Cyst, 202, 258 Cysteine, 126, 163, 164, 239, 258, 306 Cystine, 258 Cystoid, 55, 68, 258 Cytochrome, 34, 259 Cytogenetics, 259, 302 Cytokines, 175, 259, 275 Cytoplasm, 245, 247, 252, 259, 262, 265, 271, 284, 286, 301 Cytoskeleton, 259, 276

Index 319

Cytotoxic, 20, 51, 202, 259, 274, 297, 298, 304 Cytotoxins, 31, 259 D Dairy Products, 194, 259 Dark Adaptation, 58, 259 Databases, Bibliographic, 215, 259 Decidua, 259, 292 Defense Mechanisms, 259, 276 Degenerative, 21, 22, 35, 52, 56, 94, 150, 154, 170, 177, 189, 197, 259, 281, 300, 301 Deletion, 245, 259 Delusions, 259, 296 Dendrites, 260, 286 Dendritic, 260, 282, 300, 305 Density, 30, 41, 155, 249, 260, 279, 287 Dental Hygienists, 3, 4, 260 Depolarization, 260, 304 Depressive Disorder, 43, 260 Depth Perception, 260, 305 DES, 105, 158, 242, 260 Desensitization, 57, 142, 260 Detergents, 154, 260 Deuterium, 260, 273 Developed Countries, 36, 38, 49, 176, 260 Diabetes Mellitus, 58, 139, 141, 143, 164, 170, 260, 270, 272, 300 Diagnostic procedure, 137, 147, 205, 260 Dialyzer, 260, 271 Diastolic, 260, 273 Diffusion, 159, 248, 260, 271, 275, 277 Digestion, 48, 161, 185, 248, 249, 260, 280, 305, 311 Digestive system, 146, 261 Dilatation, 171, 243, 261, 311 Dilation, 132, 137, 249, 261, 311 Diploid, 261, 292 Diplopia, 91, 239, 261, 310 Direct, iii, 24, 25, 32, 36, 39, 41, 191, 209, 252, 254, 261, 290, 298, 307 Disease Progression, 169, 261 Disparity, 261, 305 Dissection, 171, 261 Dissociation, 21, 240, 261, 309 Dissociative Disorders, 261 Distal, 171, 261, 263, 296 Diurnal, 50, 261 Dopamine, 17, 190, 244, 261, 291 Dopamine Antagonists, 190, 261 Dorsal, 262, 293 Dorsum, 262, 268 Dosage Forms, 163, 262

Drive, ii, vi, 7, 107, 130, 142, 143, 262, 277, 279 Drug Design, 53, 262 Drug Interactions, 210, 262 Drusen, 5, 6, 16, 28, 36, 45, 59, 62, 64, 67, 69, 70, 71, 95, 98, 138, 177, 262 Dyes, 158, 159, 162, 247, 262, 286 Dyslexia, 167, 262 Dysphoric, 260, 262 Dyspnea, 262, 297 Dystrophic, 4, 17, 262 Dystrophy, 4, 7, 15, 32, 49, 52, 53, 59, 60, 67, 127, 131, 176, 262 E Ectopic, 163, 262 Edema, 55, 68, 133, 134, 141, 143, 182, 260, 262, 276, 284 Effector, 255, 262, 286, 291 Effector cell, 262, 286 Efficacy, 21, 28, 29, 41, 43, 45, 63, 72, 83, 129, 132, 135, 136, 143, 144, 149, 165, 169, 262 Egg Yolk, 262, 313 Elasticity, 43, 168, 246, 263, 294, 304 Elastin, 243, 255, 263, 266 Elective, 263 Electrocoagulation, 255, 263 Electrode, 131, 168, 263 Electrolyte, 241, 258, 263, 268, 283, 287, 293, 304 Electrons, 244, 247, 263, 277, 289, 297, 298 Electrophysiological, 37, 72, 263 Electroretinogram, 35, 131, 263 Electroretinography, 58, 263 Elementary Particles, 263, 286, 296 Emboli, 171, 263, 313 Embolism, 263, 297, 313 Embolization, 263, 313 Embolus, 263, 275 Embryo, 248, 252, 262, 263, 275, 287, 294 Emulsion, 263, 268 Encapsulated, 264, 279 Encephalopathy, 105, 264 Endemic, 264, 305 Endocrine Glands, 264, 272 Endocytosis, 15, 264 Endometrial, 264 Endometriosis, 172, 183, 264 Endometrium, 162, 172, 192, 259, 264, 282 Endophthalmitis, 135, 264 Endostatin, 33, 180, 264 Endothelium, 159, 264

320 Macular Degeneration

Endothelium, Lymphatic, 264 Endothelium, Vascular, 264 Endotoxic, 264, 279 Endotoxin, 264, 310 Energy balance, 264, 278 Enhancer, 42, 264 Environmental Exposure, 264, 287 Environmental Health, 214, 216, 264 Enzymatic, 16, 250, 251, 256, 265, 267, 299 Enzyme Inhibitors, 265, 292 Eosinophils, 265, 271, 278 Epidemic, 265, 305 Epidemiological, 10, 23, 24, 155, 265 Epidermis, 265, 273, 297 Epinephrine, 240, 261, 265, 286, 311 Epiretinal Membrane, 157, 265 Episcleritis, 265, 302 Epithelial Cells, 15, 27, 29, 41, 59, 68, 95, 160, 169, 265, 272, 278, 295 Epithelium, 5, 6, 8, 12, 13, 15, 16, 18, 22, 27, 29, 34, 35, 40, 41, 44, 45, 46, 49, 53, 59, 63, 75, 76, 82, 91, 95, 109, 119, 151, 156, 157, 160, 168, 175, 176, 177, 180, 185, 247, 264, 265, 277, 300, 301 Epoprostenol, 265, 274 Erectile, 43, 195, 265 Erection, 265 Erythrocyte Membrane, 155, 265 Erythrocytes, 155, 243, 249, 265, 272, 298, 299, 303 Esophagus, 261, 265, 305 Estrogen, 155, 265 Ethanolamine, 169, 265 Eukaryotic Cells, 20, 266, 275, 288, 311 Evacuation, 257, 266 Evoke, 25, 187, 266, 305 Evoked Potentials, 102, 266 Excimer laser, 85, 266 Excipient, 172, 266 Excitation, 266, 309 Excitatory, 25, 266, 270 Excitotoxicity, 163, 266 Exogenous, 7, 15, 40, 156, 158, 261, 266, 311 Extensor, 266, 296 External-beam radiation, 266, 277, 297, 313 Extracellular Matrix, 34, 166, 182, 188, 256, 266, 276, 281 Extracellular Matrix Proteins, 34, 188, 266, 281 Extracellular Space, 27, 266

Extraction, 65, 193, 245, 266, 300 Extrapyramidal, 35, 244, 261, 266 Extremity, 15, 266 Eye Infections, 240, 266 Eye Movements, 130, 134, 142, 143, 267 F Family Planning, 215, 267 Fatigue, 197, 267, 271 Fatty acids, 33, 155, 241, 267, 270, 280, 294 Feces, 257, 267 Ferritin, 122, 267 Fetus, 267, 268, 292, 294, 311 Fibrin, 184, 249, 267, 292, 308, 309 Fibrinogen, 37, 267, 292, 308 Fibrinolytic, 267, 308 Fibrinolytic Agents, 267, 308 Fibroblast Growth Factor, 21, 23, 267 Fibromuscular Dysplasia, 171, 267 Fibronectin, 267, 269 Fibrosis, 164, 180, 181, 193, 241, 267, 297, 301, 302 Fibula, 267, 293 Filtration, 100, 167, 267 Fixation, 75, 187, 267, 303 Fluid Therapy, 268, 287 Fluorescein Angiography, 94, 103, 130, 133, 137, 142, 143, 144, 268 Fluorescence, 27, 48, 268 Foetoplacental, 268, 287 Forearm, 249, 268 Fovea, 49, 139, 150, 153, 268 Fundus, 7, 19, 26, 32, 44, 45, 75, 77, 81, 122, 143, 173, 176, 268, 288 G Galactosides, 248, 268 Gallbladder, 248, 261, 268 Gamma Rays, 268, 297, 298 Ganglia, 247, 268, 285, 290 Ganglion, 39, 268, 287, 288, 300, 312 Gas, 242, 246, 250, 260, 265, 268, 273, 278, 284, 286, 306 Gastric, 251, 262, 268 Gastrin, 268, 272 Gastrointestinal, 17, 179, 206, 249, 265, 269, 278, 306, 310 Gelatin, 269, 270 Gelatinase A, 175, 269 Gene Expression, 6, 22, 30, 49, 50, 157, 185, 188, 269 Gene Products, rev, 269 Genes, env, 57, 269 Genetic Code, 269, 286

Index 321

Genetic Engineering, 248, 254, 269 Genetic Techniques, 9, 269 Genetics, 4, 11, 22, 35, 37, 48, 54, 60, 62, 77, 78, 100, 105, 259, 269 Genotype, 35, 57, 78, 269, 291 Geriatric, 43, 121, 122, 269 Gestation, 269, 290, 292 Giant Cells, 269, 301 Gigantism, 158, 269 Gland, 240, 269, 280, 289, 292, 295, 302, 305, 308 Glomerular, 269, 270 Glomeruli, 270 Glomerulonephritis, 6, 270 Glucocorticoid, 250, 270, 310 Gluconeogenesis, 270 Glucose, 51, 249, 252, 260, 270, 272, 276, 301 Glucose Intolerance, 260, 270 Glutamate, 17, 25, 266, 270 Glutathione Peroxidase, 270, 303 Glycerol, 270, 291 Glycerophospholipids, 270, 291 Glycine, 163, 164, 242, 270, 303 Glycogen, 270 Glycoprotein, 188, 267, 269, 270, 278, 284, 308, 310 Glycosaminoglycans, 266, 270 Goats, 259, 270 Gonadal, 270, 305 Governing Board, 270, 294 Grade, 45, 270, 271 Grading, 9, 18, 79, 85, 270 Graft, 12, 271, 273, 275 Graft Rejection, 12, 271, 275 Gram-negative, 258, 264, 271 Gram-Negative Bacteria, 258, 264, 271 Granulocytes, 271, 304, 313 Growth factors, 29, 34, 42, 80, 166, 175, 191, 271 H Haematoma, 271 Haemodialysis, 155, 271 Haemorrhage, 99, 271 Half-Life, 271, 274 Haploid, 271, 292 Health Education, 69, 271 Heart attack, 195, 251, 271 Heart failure, 271, 297 Hematoporphyrins, 158, 271 Heme, 242, 259, 271, 285, 293 Hemodialysis, 155, 250, 260, 271

Hemoglobin, 19, 134, 243, 265, 271, 272, 293 Hemoglobin A, 272, 293 Hemolysis, 155, 265, 272 Hemostasis, 272, 276 Hepatic, 154, 155, 241, 267, 272 Hepatocytes, 155, 272 Hereditary, 37, 56, 81, 102, 138, 199, 272, 285, 300 Heredity, 24, 41, 81, 150, 239, 269, 272 Heterodimer, 184, 272 Heterogeneity, 155, 241, 272 Heterozygotes, 57, 272 Hiccup, 262, 272 Histology, 34, 48, 272 Homeostasis, 20, 51, 162, 172, 272 Homogeneous, 38, 246, 272, 290 Homologous, 241, 269, 272, 303, 307 Hormonal, 247, 258, 272 Hormone Antagonists, 158, 272 Host, 12, 15, 27, 152, 185, 247, 265, 273, 274, 275, 278, 312 Human growth hormone, 158, 273 Humoral, 271, 273 Hybrid, 7, 254, 273 Hybridization, 186, 273 Hydrogen, 183, 239, 242, 247, 250, 260, 266, 270, 273, 279, 284, 286, 289, 296, 306 Hydrogen Peroxide, 270, 273, 279, 306 Hydrolysis, 248, 273, 277, 291, 293, 296, 309 Hydrophilic, 260, 273 Hydrophobic, 260, 270, 273, 279 Hydroxylysine, 255, 273 Hydroxyproline, 255, 273 Hypercholesterolemia, 31, 163, 273 Hyperlipoproteinemia, 273 Hyperopia, 83, 273, 298 Hyperpigmentation, 98, 273 Hypersensitivity, 241, 260, 273, 278, 301, 303 Hypertension, 19, 44, 83, 139, 140, 150, 163, 182, 246, 251, 273, 276, 300 Hypertriglyceridemia, 155, 273 Hypertrophy, 40, 76, 257, 274, 310 Hypothyroidism, 105, 274 Hypoxia, 13, 55, 160, 162, 274, 308 I Iatrogenic, 171, 274 Id, 81, 112, 121, 123, 220, 221, 223, 225, 232, 234, 274

322 Macular Degeneration

Idiopathic, 139, 141, 156, 168, 180, 267, 274, 301 Ileum, 274, 313 Iloprost, 72, 83, 274 Imidazole, 175, 274 Immune response, 161, 244, 258, 271, 274, 302, 303, 306, 312 Immune system, 248, 262, 274, 275, 279, 281, 290, 311, 313 Immunity, 259, 274, 281 Immunization, 274, 275, 303 Immunogenic, 274, 279 Immunoglobulin, 243, 274, 284 Immunohistochemistry, 12, 21, 35, 274 Immunologic, 253, 274, 281, 298 Immunosuppressive, 270, 274, 275, 302 Immunosuppressive Agents, 274, 302 Immunotherapy, 59, 84, 248, 260, 275 Impairment, 4, 13, 15, 58, 154, 156, 177, 178, 191, 198, 246, 267, 275, 282, 296 Implant radiation, 275, 276, 277, 297, 314 Implantation, 275, 287 Impotence, 195, 265, 275 In situ, 33, 40, 275 In Situ Hybridization, 33, 275 In vitro, 5, 6, 8, 11, 14, 15, 16, 20, 29, 33, 43, 48, 57, 155, 172, 175, 189, 275 Incision, 275, 277 Indicative, 160, 196, 275, 289, 311 Induction, 7, 243, 244, 275 Infarction, 90, 139, 275 Infection, 20, 86, 99, 161, 174, 248, 253, 257, 266, 275, 280, 281, 286, 301, 306, 313 Infertility, 275, 277 Infiltration, 270, 275 Infusion, 249, 275 Ingestion, 49, 193, 194, 276 Initiation, 276, 309 Inotropic, 261, 276 Insight, 9, 16, 22, 50, 52, 77, 276 Insomnia, 195, 276 Instillation, 159, 276 Insulin, 84, 139, 164, 276, 311 Insulin-dependent diabetes mellitus, 276 Integrins, 184, 187, 188, 276 Intermittent, 268, 276, 280 Internal radiation, 276, 277, 297, 314 Interstitial, 249, 266, 269, 276, 277, 314 Interstitial Collagenase, 269, 276 Intestinal, 154, 155, 251, 276 Intestines, 267, 269, 276, 303

Intracellular, 8, 25, 34, 48, 152, 252, 269, 275, 276, 282, 293, 295, 302, 303 Intracellular Membranes, 276, 282 Intracranial Hypertension, 239, 276, 308 Intramuscular, 276, 310 Intraocular, 21, 85, 111, 135, 164, 174, 182, 190, 264, 276, 287 Intraocular pressure, 135, 164, 182, 276, 287 Intravenous, 249, 268, 276, 277 Intrinsic, 15, 22, 27, 241, 247, 277 Invasive, 13, 159, 182, 274, 277, 281 Involuntary, 187, 247, 277, 285, 298 Ion Channels, 50, 246, 277, 286 Ion Transport, 277, 283 Ionizing, 241, 264, 277, 298 Ions, 182, 247, 250, 253, 261, 263, 273, 277, 282, 304 Iris, 23, 59, 76, 140, 160, 178, 243, 253, 257, 277, 297, 311 Irradiation, 70, 73, 277, 314 Irritants, 135, 190, 277 Ischemia, 13, 17, 160, 177, 239, 247, 277 Isotretinoin, 60, 101, 277 K Kallikreins, 169, 277 Kb, 214, 278 Kinetics, 22, 47, 250, 278 Krypton, 87, 139, 143, 278 L Labile, 255, 278 Lactation, 278, 287 Laminin, 247, 266, 278 Large Intestine, 261, 276, 278, 298, 304 Laser Surgery, 201, 278 Laser therapy, 157, 236, 278 Latent, 278, 294 Least-Squares Analysis, 278, 299 Lectin, 278, 282 Legal blindness, 18, 54, 138, 176, 179, 278 Lens, 30, 33, 34, 55, 130, 133, 134, 137, 138, 142, 143, 150, 173, 178, 245, 251, 278, 294, 313 Leptin, 99, 278 Lesion, 72, 83, 103, 111, 139, 159, 278, 280 Lethal, 52, 278, 284 Lethargy, 274, 278 Leukocytes, 192, 247, 249, 253, 259, 265, 271, 278, 284, 286, 310 Leukotrienes, 245, 246, 278 Levo, 163, 279 Libido, 195, 243, 279

Index 323

Library Services, 232, 279 Lidocaine, 248, 279 Ligament, 279, 295 Ligands, 42, 149, 165, 276, 279 Likelihood Functions, 279, 299 Linear Models, 279, 299 Linkage, 16, 19, 24, 46, 54, 60, 78, 279 Linkage Disequilibrium, 19, 279 Lipid, 10, 35, 42, 45, 48, 51, 65, 93, 155, 163, 245, 246, 253, 270, 276, 279, 289, 310 Lipid A, 155, 279 Lipid Peroxidation, 35, 65, 93, 279, 289 Lipofuscin, 5, 35, 48, 49, 59, 60, 64, 76, 101, 131, 185, 253, 279 Lipopolysaccharides, 279 Lipoprotein, 86, 155, 271, 279, 280 Liposomal, 164, 279 Liposome, 15, 279 Lipoxygenase, 33, 245, 278, 280 Liver scan, 280, 302 Lobe, 273, 280 Lobsters, 10, 280 Localization, 34, 36, 40, 45, 79, 186, 274, 280 Localized, 6, 171, 186, 242, 264, 268, 271, 275, 278, 280, 292, 302 Locomotion, 280, 292 Logistic Models, 280, 299 Long-Term Care, 20, 58, 280 Loop, 26, 280 Low vision, 4, 25, 47, 89, 223, 224, 280 Low-density lipoprotein, 163, 279, 280 Lumen, 171, 182, 192, 264, 280 Lymph, 247, 254, 258, 264, 280, 281, 301 Lymph node, 247, 280, 281, 301 Lymphatic, 154, 264, 275, 280, 304, 305, 308 Lymphatic system, 280, 304, 305, 308 Lymphocyte, 244, 281, 282 Lymphoid, 244, 281 Lymphokines, 281 M Macrophage, 28, 281 Macrophage Activation, 28, 281 Macula Lutea, 161, 187, 281 Magnetic Resonance Imaging, 281 Malignant, 26, 156, 159, 244, 246, 281, 285, 295, 298 Malnutrition, 241, 247, 281 Mammogram, 250, 281, 283 Mandible, 242, 281, 299 Manic, 244, 281, 296

Manic-depressive psychosis, 281, 296 Manifest, 21, 281, 306 Matrix metalloproteinase, 73, 174, 281 Meat, 194, 281 Medial, 10, 171, 246, 281, 288 Mediate, 10, 20, 36, 184, 188, 261, 281 Mediator, 34, 160, 282 Medicament, 183, 282 MEDLINE, 215, 282 Melanin, 192, 277, 282, 291, 311 Melanocytes, 273, 282 Melanoma, 26, 282 Membrane Glycoproteins, 282 Membrane Potentials, 38, 282 Membrane Proteins, 52, 282 Menopause, 124, 155, 195, 282, 287, 293 Menstrual Cycle, 282, 287, 294 Menstruation, 259, 282 Mental Disorders, 146, 282, 296 Mental Health, iv, 4, 136, 146, 214, 217, 282, 296 Mental Processes, 261, 282, 296 Metastasis, 53, 152, 153, 163, 166, 173, 182, 184, 188, 281, 282 Metastasize, 173, 282, 302 Metastatic, 148, 149, 165, 169, 282, 302 MI, 110, 237, 282 Microbe, 283, 309 Microbiology, 240, 283 Microcalcifications, 250, 283 Microgram, 16, 283 Micronutrients, 46, 283 Microorganism, 255, 283, 313 Microscopy, 16, 21, 41, 48, 161, 185, 247, 283 Midaxillary line, 283, 313 Migration, 53, 152, 153, 166, 182, 184, 188, 281, 283 Milligram, 283 Millimeter, 283, 313 Mineralocorticoids, 182, 240, 258, 283 Minority Groups, 19, 283 Mitochondria, 33, 283, 288 Mitochondrial Swelling, 283, 285 Mitosis, 152, 192, 245, 283 Mitotic, 51, 283 Mobility, 7, 25, 45, 103, 283 Modeling, 262, 283 Modification, 10, 164, 269, 283, 297 Monitor, 19, 40, 189, 284, 286 Monoclonal, 52, 158, 277, 284, 297, 314 Monoclonal antibodies, 52, 284

324 Macular Degeneration

Monocytes, 28, 278, 284 Mononuclear, 284, 310 Monotherapy, 63, 284 Morphogenesis, 52, 284 Morphological, 37, 263, 282, 284 Morphology, 39, 67, 72, 75, 157, 251, 281, 284 Mucinous, 268, 284 Mucolytic, 239, 284 Muscular Dystrophies, 262, 284 Musculature, 267, 284 Mustard Gas, 277, 284 Mutagenesis, 53, 284 Mutagens, 284 Mydriatic, 261, 284 Myocardial infarction, 17, 245, 257, 282, 284, 313 Myocardium, 282, 284, 285 Myoglobin, 285, 293 Myopia, 156, 164, 168, 180, 181, 193, 285, 298, 300 N N-acetyl, 126, 163, 164, 239, 270, 285 Nausea, 244, 245, 262, 285 NCI, 1, 145, 213, 254, 285 Nearsightedness, 285 Necrosis, 171, 245, 257, 264, 275, 282, 284, 285, 301 Neomycin, 15, 285 Neonatal, 52, 285 Neoplasia, 285 Neoplasm, 285, 289, 311 Neoplastic, 111, 163, 183, 285 Nephropathy, 15, 158, 170, 285 Nerve Fibers, 35, 285, 288 Nerve Regeneration, 36, 285 Nervous System, 170, 240, 252, 254, 282, 285, 286, 290, 306 Neural, 12, 27, 36, 51, 58, 160, 161, 181, 240, 273, 285, 300, 304 Neurodegenerative Diseases, 164, 247, 285 Neuronal, 25, 36, 51, 163, 250, 254, 286 Neurons, 11, 25, 35, 41, 260, 266, 268, 285, 286, 307, 312 Neuropathy, 170, 286 Neuropeptides, 50, 286 Neuroretinitis, 286, 300 Neurotransmitters, 25, 286 Neutrons, 241, 277, 286, 297 Neutrophils, 245, 271, 278, 286 Night Blindness, 178, 286, 300

Nitrogen, 183, 242, 243, 246, 258, 266, 268, 286, 310 Nonverbal Communication, 286, 296 Norepinephrine, 240, 261, 286 Nuclear, 42, 46, 83, 247, 263, 266, 268, 269, 285, 286, 300 Nuclei, 241, 263, 269, 281, 283, 286, 287, 288, 296, 312 Nucleic acid, 177, 185, 186, 189, 247, 269, 273, 275, 284, 286 Nucleic Acid Hybridization, 273, 286 Nutritional Support, 9, 287 Nystagmus, 94, 187, 287 O Occipital Lobe, 261, 287, 312 Occult, 18, 56, 61, 79, 87, 91, 98, 101, 287 Ocular Hypertension, 55, 182, 190, 287 Oculomotor, 261, 287 Oculomotor Nerve, 261, 287 Oestrogen, 78, 287 Ointments, 262, 287 Oncogene, 35, 287 Oncogenic, 276, 287 Opacity, 251, 260, 287 Operon, 287, 299 Ophthalmologist, 44, 51, 287 Ophthalmoscope, 133, 287, 288 Ophthalmoscopy, 69, 288 Opsin, 288, 299, 300 Optic Chiasm, 288 Optic Disk, 260, 281, 288 Optic Nerve, 36, 163, 164, 182, 262, 286, 288, 299, 300, 302 Optic Nerve Diseases, 288, 302 Optic nerve head, 164, 262, 286, 288 Orbit, 154, 239, 288, 310 Orbital, 154, 239, 288, 310 Organelles, 33, 259, 282, 284, 288, 292, 299 Osmosis, 288 Osmotic, 100, 241, 283, 288 Osteoarthritis, 171, 195, 288 Osteoclasts, 148, 288 Osteoporosis, 148, 149, 155, 165, 188, 195, 287, 288 Ovarian Follicle, 257, 288 Ovary, 257, 287, 288, 289 Ovulation, 166, 289 Ovum, 258, 259, 269, 288, 289, 294 Oxidants, 155, 194, 289 Oxidation, 21, 45, 155, 204, 239, 244, 245, 258, 259, 270, 279, 289 Oxidation-Reduction, 289

Index 325

Oxidative Stress, 16, 20, 36, 46, 49, 70, 109, 163, 289 Oxygenation, 55, 289 P Palliative, 287, 289, 308 Pancreas, 248, 261, 276, 289, 310 Pancreatic, 251, 289 Papilloma, 289, 300 Parotid, 289, 301 Particle, 279, 289, 309 Patch, 49, 289 Pathogenesis, 5, 6, 9, 21, 29, 36, 40, 45, 49, 53, 55, 56, 62, 71, 85, 110, 122, 157, 180, 202, 289 Pathologic, 23, 27, 32, 36, 60, 136, 141, 156, 162, 168, 180, 245, 257, 273, 289, 290, 296, 299, 311 Pathologic Processes, 245, 290 Pathologies, 4, 14, 27, 88, 290 Pathophysiology, 24, 35, 51, 290 Patient Education, 69, 201, 222, 223, 230, 232, 237, 290 Pedigree, 24, 81, 290 Pelvic, 264, 290, 295 Peptide, 60, 172, 267, 278, 290, 293, 295, 296, 308 Perception, 26, 141, 150, 256, 260, 290 Perforation, 245, 290 Perfusion, 93, 100, 164, 274, 290 Pericytes, 192, 290 Perimetry, 76, 141, 189, 290 Perinatal, 166, 290 Peripheral Nervous System, 285, 290, 306 Peripheral vision, 290, 313 Petechiae, 271, 290 Phagocyte, 289, 290 Phagocytosis, 49, 161, 290 Phallic, 268, 290 Pharmaceutical Solutions, 262, 290 Pharmacokinetic, 45, 290 Pharmacologic, 137, 243, 271, 291, 309 Phenotype, 4, 5, 6, 11, 23, 35, 37, 40, 78, 80, 158, 291 Phenylalanine, 291, 311 Phosphodiesterase, 291, 309 Phospholipases, 291, 304 Phospholipids, 45, 48, 155, 168, 185, 267, 279, 291 Phosphorus, 250, 291 Phosphorylated, 255, 291 Phosphorylation, 36, 192, 291

Photoreceptor, 4, 6, 9, 11, 20, 21, 22, 30, 33, 35, 37, 41, 42, 49, 50, 51, 52, 53, 56, 57, 142, 150, 161, 185, 291 Photosensitizer, 180, 291 Photosensitizing Agents, 291, 293 Phototransduction, 40, 51, 52, 291, 302 Physical Examination, 130, 131, 137, 142, 143, 291 Physiologic, 241, 248, 271, 282, 283, 291, 294, 298, 299 Physiology, 27, 31, 50, 85, 93, 163, 194, 263, 291 Pigmentation, 273, 292 Pilot study, 26, 47, 61, 74, 77, 89, 91, 112, 292 Pituitary Gland, 258, 267, 292 Placenta, 152, 192, 268, 292, 294 Plants, 8, 250, 253, 254, 259, 270, 278, 284, 286, 292, 293, 301, 309, 310 Plaque, 10, 94, 170, 174, 292 Plasma cells, 244, 292 Plasma Kallikrein, 277, 292 Plasma protein, 166, 241, 264, 292 Plasma Volume, 283, 292 Plasmid, 41, 292, 311 Plasmin, 267, 292, 309, 311 Plasminogen, 267, 292, 309, 311 Plastids, 288, 292 Platelet Activation, 292, 304 Platelet Aggregation, 242, 265, 274, 293, 308 Platelets, 184, 245, 292, 293, 308 Platinum, 280, 293 Polychromatic, 30, 293 Polymerase, 293, 299 Polymorphic, 132, 293 Polypeptide, 242, 255, 267, 273, 285, 292, 293, 295, 314 Polysaccharide, 244, 252, 293, 295 Polyunsaturated fat, 293, 308 Pons, 239, 249, 293, 301 Popliteal, 171, 293 Porfimer sodium, 158, 293 Porphyrins, 158, 164, 293 Posterior, 55, 88, 135, 139, 159, 164, 242, 246, 253, 262, 277, 283, 287, 289, 293, 302 Postmenopausal, 44, 155, 288, 293 Postnatal, 293, 305 Postsynaptic, 293, 304, 307 Potassium, 25, 182, 241, 282, 283, 293 Potentiation, 294, 304 Practice Guidelines, 217, 223, 294

326 Macular Degeneration

Preclinical, 45, 47, 95, 294 Precursor, 245, 248, 261, 262, 265, 286, 291, 292, 294, 310, 311 Predisposition, 162, 171, 294 Prenatal, 35, 263, 294 Prenatal Diagnosis, 35, 294 Presbyopia, 150, 154, 294 Presynaptic, 17, 294, 307 Prevalence, 19, 185, 294 Primary tumor, 152, 153, 294 Prodrug, 294 Progesterone, 294, 305 Progressive disease, 22, 294 Projection, 259, 286, 288, 294, 298 Proline, 255, 273, 294 Promoter, 7, 41, 52, 294 Prophylaxis, 153, 260, 294, 313 Proportional, 4, 294 Prostaglandin, 16, 265, 294, 308 Prostaglandins A, 17, 295 Prostaglandins D, 295 Prostate, 14, 195, 248, 277, 287, 295, 310 Prostate-Specific Antigen, 277, 295 Protease, 21, 295, 309 Protein C, 73, 127, 241, 242, 245, 247, 267, 279, 295 Protein Conformation, 242, 295 Protein S, 192, 198, 248, 269, 273, 285, 295, 301, 307 Protein Transport, 37, 295 Proteoglycans, 247, 266, 295 Proteolytic, 20, 152, 182, 255, 267, 277, 292, 296, 309, 311 Protocol, 10, 15, 41, 136, 296 Protons, 38, 148, 241, 273, 277, 296, 297 Proximal, 161, 261, 294, 296 Pseudoxanthoma, 17, 296 Pseudoxanthoma Elasticum, 17, 296 Psoriasis, 152, 163, 166, 172, 183, 284, 291, 296 Psychiatry, 43, 120, 122, 123, 267, 296 Psychic, 279, 296 Psychology, 261, 296 Psychosis, 122, 244, 296 Psychotherapy, 43, 136, 296 Puberty, 296 Public Health, 10, 19, 24, 38, 44, 199, 217, 296 Public Policy, 215, 296 Publishing, 59, 296 Pulmonary, 43, 171, 249, 257, 265, 278, 297, 306, 312, 313

Pulmonary Artery, 249, 297, 312 Pulmonary Embolism, 297, 313 Pulmonary Fibrosis, 43, 171, 297 Pulmonary hypertension, 257, 265, 297 Pulse, 134, 263, 284, 297 Pupil, 26, 30, 178, 187, 253, 257, 261, 284, 297 Purpura, 271, 297 Purulent, 264, 297 Pyramidal Tracts, 266, 297 Q Quality of Life, 29, 43, 58, 65, 70, 98, 127, 141, 297 Quiescent, 172, 297 R Race, 177, 283, 297 Radiation therapy, 89, 90, 97, 239, 266, 276, 277, 297, 314 Radioactive, 249, 271, 273, 275, 276, 277, 280, 284, 286, 287, 297, 302, 314 Radioimmunotherapy, 297, 298 Radiolabeled, 277, 297, 314 Radiotherapy, 67, 74, 89, 90, 94, 97, 99, 102, 104, 110, 249, 277, 297, 298, 307, 314 Randomized, 43, 46, 61, 73, 92, 96, 98, 103, 104, 118, 135, 137, 139, 140, 141, 144, 262, 298 Randomized clinical trial, 61, 73, 103, 118, 137, 298 Reaction Time, 84, 298 Reagent, 14, 265, 298 Reality Testing, 296, 298 Recombinant, 11, 14, 40, 45, 47, 53, 56, 83, 152, 184, 185, 298, 311 Reconstitution, 176, 298 Rectum, 249, 261, 268, 278, 295, 298 Recurrence, 84, 85, 254, 281, 298 Red blood cells, 33, 265, 298, 301 Red Nucleus, 246, 298 Refer, 1, 255, 268, 280, 281, 286, 296, 297, 298 Reflex, 187, 267, 298 Refraction, 173, 235, 285, 298, 305 Refractive Errors, 261, 298 Refractive Power, 173, 285, 298 Regeneration, 20, 35, 267, 298 Regimen, 160, 262, 298, 301 Regression Analysis, 25, 299 Rehabilitative, 19, 299 Remission, 281, 298, 299 Repressor, 20, 36, 42, 287, 299 Research Design, 38, 49, 299

Index 327

Residual disease, 169, 299 Resorption, 148, 288, 299 Respiration, 250, 284, 299 Restoration, 298, 299, 313 Reticulocytes, 33, 299 Retinae, 17, 281, 299 Retinal Detachment, 9, 27, 33, 41, 135, 162, 177, 260, 300 Retinal Ganglion Cells, 35, 288, 300 Retinal Hemorrhage, 17, 300 Retinal Neovascularization, 33, 44, 55, 172, 300 Retinal Vein, 55, 135, 153, 300 Retinal Vein Occlusion, 55, 135, 153, 300 Retinal Vessels, 160, 300 Retinaldehyde, 5, 40, 288, 300 Retinitis, 4, 7, 11, 15, 21, 22, 33, 35, 37, 41, 42, 50, 56, 61, 178, 300, 301 Retinitis Pigmentosa, 4, 7, 11, 15, 21, 22, 33, 35, 37, 41, 42, 50, 61, 178, 300 Retinoblastoma, 20, 300 Retinoblastoma Protein, 20, 300 Retinoid, 40, 53, 300 Retinol, 41, 299, 300 Retreatment, 179, 301 Retrobulbar, 67, 301 Rheumatism, 301 Rheumatoid, 152, 153, 171, 183, 184, 188, 255, 289, 301 Rheumatoid arthritis, 152, 153, 171, 183, 184, 188, 255, 301 Ribose, 240, 301 Ribosome, 301, 309 Rigidity, 167, 292, 301 Rod, 4, 22, 32, 35, 39, 45, 46, 49, 51, 52, 56, 57, 142, 157, 161, 254, 291, 301, 309 Rod cells, 161, 301, 309 Rod Outer Segments, 49, 157, 301 Rose Bengal, 158, 301 Rubber, 34, 239, 301 S Salivary, 261, 301 Salivary glands, 261, 301 Saponins, 301, 305 Sarcoidosis, 55, 301 Satellite, 13, 301 Scans, 10, 24, 302 Scatter, 141, 143, 302 Sclera, 167, 253, 256, 265, 302, 311 Scleritis, 55, 302 Sclerosis, 246, 255, 302 Scotoma, 98, 164, 181, 193, 302

Screening, 24, 32, 35, 43, 53, 57, 77, 131, 134, 136, 170, 181, 186, 223, 254, 302 Sebaceous, 277, 302 Sebaceous gland, 277, 302 Second Messenger Systems, 286, 302 Secondary tumor, 282, 302 Secretion, 27, 50, 154, 155, 158, 239, 254, 258, 274, 276, 278, 283, 302, 303, 311 Secretory, 37, 148, 302, 307 Segmental, 267, 303 Segmentation, 69, 303 Selenium, 114, 140, 303 Self Care, 239, 303 Semen, 295, 303 Senescence, 35, 189, 303 Senile, 81, 87, 101, 105, 122, 139, 197, 198, 199, 244, 288, 303 Sensitization, 142, 303 Sensor, 26, 40, 303 Sequence Analysis, 35, 303 Serine, 169, 277, 295, 303, 309 Serous, 68, 156, 264, 303 Serum, 86, 99, 122, 155, 241, 242, 255, 256, 280, 283, 298, 303, 310 Sex Characteristics, 243, 287, 296, 303 Sharpness, 303, 312 Shock, 303, 310 Side effect, 21, 99, 132, 134, 142, 160, 179, 191, 209, 240, 244, 245, 248, 303, 309 Signal Transduction, 42, 191, 303 Skeletal, 243, 254, 284, 304 Skeleton, 239, 295, 304 Skin Aging, 189, 304 Skull, 258, 288, 304, 307 Small intestine, 248, 253, 272, 274, 276, 304 Smooth muscle, 241, 242, 256, 277, 290, 304, 306 Social Environment, 297, 304 Sodium, 137, 142, 182, 241, 265, 282, 283, 291, 304, 309 Sodium Channels, 291, 304 Soft tissue, 249, 304 Solid tumor, 54, 152, 153, 173, 243, 264, 304 Solvent, 193, 270, 288, 290, 304 Somatic, 273, 283, 290, 304 Somatic cells, 283, 304 Specialist, 111, 226, 261, 304 Species, 8, 241, 242, 252, 265, 273, 283, 284, 297, 304, 306, 310, 312, 313 Spectrometer, 27, 305 Spectrum, 12, 28, 30, 186, 305

328 Macular Degeneration

Sperm, 243, 253, 305 Spike, 25, 305 Spinal cord, 246, 249, 252, 253, 268, 285, 286, 290, 297, 298, 305 Spleen, 242, 280, 301, 305 Sporadic, 50, 285, 300, 305 Stabilization, 10, 56, 305 Staging, 162, 171, 302, 305 Steel, 254, 305 Stem Cells, 11, 182, 305 Stereoscopic, 122, 305 Sterile, 176, 305 Steroid, 142, 174, 287, 301, 305 Stimulants, 192, 305 Stimulus, 6, 167, 182, 188, 262, 263, 266, 277, 298, 305, 308 Stomach, 261, 265, 268, 269, 272, 276, 285, 304, 305 Strabismus, 261, 305 Strand, 163, 293, 306 Stress, 14, 20, 49, 51, 95, 251, 285, 289, 294, 301, 306 Stroke, 146, 195, 214, 251, 306 Stroma, 277, 306 Stromal, 264, 306 Styrene, 301, 306 Subacute, 275, 306 Subclinical, 139, 275, 306 Subconjunctival, 55, 306 Subcutaneous, 240, 262, 306, 313 Subspecies, 304, 306 Substance P, 298, 302, 306 Substrate, 11, 21, 192, 265, 306 Suction, 267, 306 Sulfur, 266, 306 Superoxide, 78, 163, 306 Superoxide Dismutase, 78, 306 Supplementation, 60, 62, 68, 104, 108, 109, 118, 119, 120, 123, 131, 140, 155, 306 Suppression, 36, 258, 306 Surfactant, 265, 306 Sympathomimetic, 261, 265, 286, 306 Symphysis, 295, 307 Synapses, 286, 305, 307 Synaptic, 304, 307 Synergistic, 5, 40, 307 Systolic, 273, 307 T Tamponade, 157, 307 Taurine, 12, 307 Tear Gases, 277, 307 Telencephalon, 247, 307

Teletherapy, 104, 307 Telomere, 189, 307 Temporal, 30, 46, 50, 150, 281, 307 Teratogenic, 277, 307 Testis, 287, 307 Tetracycline, 30, 307 Thalamic, 246, 307 Thalamic Diseases, 246, 307 Therapeutics, 122, 170, 171, 176, 210, 308 Thermal, 164, 181, 193, 261, 286, 308 Thorax, 239, 308 Threshold, 167, 273, 308 Thrombin, 267, 293, 295, 308 Thrombocytes, 293, 308 Thrombolytic, 85, 292, 308 Thrombolytic Therapy, 85, 308 Thrombomodulin, 295, 308 Thrombosis, 153, 276, 295, 306, 308 Thromboxanes, 17, 246, 308 Thrombus, 171, 257, 275, 293, 308, 312 Thymus, 274, 280, 281, 308 Thyroid, 274, 308, 311 Thyrotropin, 274, 308 Tinnitus, 195, 308, 312 Tissue, 5, 6, 10, 12, 16, 17, 22, 27, 32, 34, 35, 51, 55, 70, 85, 88, 134, 142, 148, 159, 162, 164, 167, 172, 173, 179, 181, 184, 185, 189, 192, 193, 194, 239, 240, 243, 244, 245, 247, 248, 249, 250, 253, 254, 255, 256, 257, 259, 260, 262, 263, 264, 265, 266, 267, 271, 274, 275, 276, 277, 278, 279, 280, 281, 282, 285, 286, 290, 291, 292, 295, 296, 298, 299, 302, 303, 304, 306, 307, 308, 309, 310, 311, 313 Tissue Plasminogen Activator, 88, 309 Tomograph, 130, 309 Tomography, 39, 75, 79, 130, 256, 309 Tonicity, 272, 309 Tonometer, 133, 309 Tooth Loss, 195, 309 Tooth Preparation, 240, 309 Topical, 41, 154, 159, 190, 273, 277, 309 Torsion, 91, 275, 309 Toxic, iv, 5, 159, 177, 193, 259, 262, 264, 274, 286, 303, 306, 309 Toxicity, 15, 29, 85, 135, 262, 309 Toxicology, 216, 309 Toxins, 244, 250, 275, 284, 297, 309, 312 Traction, 254, 309 Transcription Factors, 7, 20, 42, 53, 309 Transducin, 21, 309 Transduction, 9, 21, 152, 192, 304, 309

Index 329

Transfection, 7, 15, 20, 73, 248, 309 Translation, 15, 269, 285, 309 Translocation, 12, 63, 72, 76, 84, 88, 90, 91, 94, 98, 202, 204, 295, 310 Transmitter, 246, 261, 277, 282, 286, 307, 310 Transplantation, 11, 12, 14, 20, 59, 85, 161, 189, 274, 310 Transversion, 153, 310 Trauma, 157, 171, 177, 182, 285, 310 Trees, 242, 301, 310 Triamcinolone Acetonide, 61, 72, 85, 97, 135, 310 Tricuspid Atresia, 257, 310 Triglyceride, 155, 273, 310 Trochlear Nerve, 261, 310 Trochlear Nerve Diseases, 261, 310 Trophic, 175, 310 Tryptophan, 255, 310 Tuberculosis, 257, 310 Tumor marker, 248, 310 Tumor Necrosis Factor, 37, 310 Tumor suppressor gene, 300, 310 Tumour, 166, 268, 311 Type 2 diabetes, 134, 311 Tyrosine, 42, 152, 183, 191, 261, 311 U Ubiquitin, 20, 311 Unconscious, 259, 274, 311 Urethra, 295, 311 Urinary, 102, 309, 311 Urinary Plasminogen Activator, 309, 311 Urine, 14, 248, 277, 311 Uterus, 257, 259, 264, 268, 282, 294, 307, 311 Uvea, 178, 264, 311 Uveitis, 55, 311 V Vaccine, 296, 311 Vacuoles, 264, 288, 311 Vagina, 260, 282, 307, 311 Vascular endothelial growth factor, 7, 27, 33, 55, 63, 152, 311 Vasoconstriction, 164, 265, 311 Vasodilation, 274, 311 Vasodilator, 163, 249, 261, 311 Vector, 47, 177, 309, 311 Vein, 130, 132, 133, 134, 137, 141, 142, 159, 243, 277, 286, 289, 300, 301, 311, 312

Venoms, 259, 312 Venous, 251, 295, 310, 312, 313 Venous Thrombosis, 312, 313 Ventricle, 247, 257, 297, 307, 310, 312 Ventricular, 257, 310, 312 Venules, 249, 250, 264, 312 Vesicular, 295, 312 Vestibulocochlear Nerve, 308, 312 Vestibulocochlear Nerve Diseases, 308, 312 Veterinary Medicine, 215, 312 Vial, 174, 312 Viral, 20, 148, 175, 177, 239, 257, 269, 287, 309, 312 Viral vector, 175, 177, 312 Virulence, 309, 312 Virus, 56, 247, 264, 269, 292, 300, 309, 312 Viscosity, 239, 312 Visual Cortex, 261, 312 Visual field, 44, 131, 143, 163, 188, 189, 236, 278, 288, 290, 300, 302, 312 Visual Perception, 167, 313 Vitamin A, 108, 118, 119, 138, 154, 300, 313 Vitreous Body, 253, 299, 313 Vitreous Hemorrhage, 141, 260, 313 Vitreous Humor, 150, 300, 313 Vitro, 5, 15, 17, 313 Vivo, 5, 12, 14, 15, 16, 20, 25, 27, 29, 33, 38, 39, 41, 43, 47, 55, 149, 155, 165, 175, 189, 275, 289, 308, 313 Volition, 277, 313 W Waist circumference, 96, 313 Warfarin, 89, 313 Weight-Bearing, 288, 313 White blood cell, 244, 278, 280, 281, 292, 313 Wound Healing, 162, 166, 170, 172, 182, 192, 243, 267, 276, 281, 313 X Xanthophyll, 8, 313 Xenograft, 47, 243, 313 X-ray, 243, 256, 268, 277, 281, 286, 297, 298, 302, 309, 313 X-ray therapy, 277, 313 Y Yeasts, 291, 314 Z Zymogen, 295, 314

330 Macular Degeneration

Index 331

332 Macular Degeneration

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