The Blood-Retinal Barriers PDF
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The Blood-Retinal Barriers NATO ADVANCED STUDY INSTITUTES SERIES A series of edited volumes comprising multifaceted studies of contem porary scientific issues by some of the best scientific minds in the world, assembled in cooperation with NATO Scientific Affairs Division. Series A: Life Sciences Recent Volumes in this Series Volume 22 -Plant Regulation and World Agriculture edited by Tom K. Scott Volume 23 - The Molecular Biology of Picornaviruses edited by R. Perez-Bercoff Volume 24 - Humoral Immunity in Neurological Diseases edited by D. Karcher, A. Lowenthal, and A. D. Strosberg Volume 25 - Synchrotron Radiation Applied to Biophysical and Biochemical Research edited by A. Castellani and I. F. Quercia Volume 26 -Nucleoside Analogues: Chemistry, Biology, and Medical Applications edited by RichardT. Walker, Erik DeClercq, and Fritz Eckstein Volume 27 -Developmental Neurobiology of Vision edited by Ralph D. Freeman Volume 28 - Animal Sonar Systems edited by Rene-Guy Busnel and James F. Fish Volume 29 - Genome Organization and Expression in Plants edited by C. J. Leaver Volume 30 - Human Physical Growth and Maturation edited by Francis E. Johnston, Alex F. Roche, and Charles Susanne Volume 31 - Transfer of Cell Constituents into Eukaryotic Cells edited by J. E. Celis, A. Graessmann, and A. Loyter Volume 32 -The Blood-Retinal Barriers edited by Jose G. Cunha-Vaz Volume 33 - Photoreception and Sensory Transduction in Aneural Organisms edited by Francesco Lenci and Giuliano Colombetti The series is published by an international board of publishers in con junction with NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics London and New York c Mathematical and D. Reidel Publishing Company Physical Sciences Dordrecht, Boston and London D Behavioral and Sijthoff & Noordhoff International Social Sciences Publishers E Applied Sciences Alphen aan den Rijn, The Netherlands, and Germantown U.S.A. The Blood-Retinal Barriers Edited by Jose G. Cunha-Vaz Abraham Lincoln School of Medicine, University of Illinois College of Medicine and University of Illinois Eye and Ear Infirmary, Chicago, Illinois and University of Coimbra, Portugal SPRINGER SCIENCE+BUSINESS MEDIA, LLC Library of Congress Cataloging in Publication Data Nato Advanced Study Institute on the Blood-Retinal Barriers, Espinho, Portugal, 1979. The blood-retinal barriers. (NATO advanced study institutes series: Series A, Life sciences; v. 32) Includes index. 1. Retina-Blood-vessels-Permeability. 2. Blood-brain barrier. 3. Biological transport. 4. Retina-Blood-vessels-Diseases. I. Cunha-Vaz, Jose G. II. North Atlantic Treaty Organiza tion. III. Title. IV. Series. QP479.N37 1979 617.7'3 80-10517 ISBN 978-1-4757-4657-0 ISBN 978-1-4757-4655-6 (eBook) DOI 10.1007/978-1-4757-4655-6 Lectures presented at a NATO Advanced Study Institute on the Blood-Retinal Barriers, held in Espinho, Portugal, September 10-19, 1979 © 1980 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1980 Softcover reprint of the hardcover 1st edition 1980 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfihning, recording, or otherwise, without written permission from the publisher PREFACE The concept of a blood~retinal barrier is still relatively new in the ophthalmic literature. ~fuereas work on the blood-brain barrier was initiated in the first decade of this century, the blood retinal barrier has only recently been defined. Information accu mulated during the last 10 years has shown that the function of the blood-ocular barriers may be better understood if two main barrier systems are considered to exist in the eye. The blood-aqueous barrier regulates the exchanges between the blood and the intraocu lar fluids, and the blood-retinal barrier separates the neural tissue from the blood. Recent studies have shown that the blood-retinal barrier plays a fundamental role in controlling the microenvironment of the retina. Similarly, the significance of the blood-retinal barrier in retinal disease has become increasingly clear. Fluorescein angiography has demonstrated an intricate series of relationships between altera tions of the blood-retinal barrier and diverse retinal diseases, particularly vascular retinopathies and pigment epitheliopathies. Finally, in the past few years, vitreous fluorophotometry has pro vided a new and accurate index of the alteration of the blood-retinal barrier. The blood-retinal barrier is a rapidly developing field of research. It is at a stage now in which the number of research workers is growing very fast but the information available is still dispersed. There is, therefore, a need for a reference book on the blood-retinal barriers that gives an integrated review of the new information available on the anatomy, ultrastructure, biochemistry, physiology, and pathophysiology of the blood-retinal barrier. This would be particularly useful not only for those currently working in this field, but for others who are attempting their first steps in this area of research. There is also a need to review the present knowledge on the blood-retinal barriers under the light of the available information on the blood-brain barrier. These barrier systems have many similarities, but whereas the blood-brain barrier shows a much greater wealth of research work, the blood-retinal barrier offers a different approach to examine similar problems. v vi PREFACE Communication between research workers in these areas is evidently of mutual interest. These were the main objectives of the Advanced Study Institute on "the Blood-Retinal Barriers" that was held in Espinho, Portugal, from September 10 to September 19, 1979. This book is comprised of the lectures given at the meeting. The first chapter reviews the basic mechanism of membrane permeability. It examines biochemical aspects, with special empha sis on active transport, followed by a review on the mathematical analysis of the passive mechanisms. The second chapter explores the sites and functions of the blood-brain and blood-retinal barriers, particularly the morpholo gical aspects of the barriers. The physiology and pharmacology of both barriers are then con sidered at some length, with particular emphasis on the re·lationship of the blood-retinal barriers with intraocular fluid dynamics. The role the blood-retinal barrier takes in maintaining retinal homeo stasis opens an entirely new and extensive area of research. The methods available to examine barrier permeability are critically evaluated. Fluorescein angiography has proved invaluable in showing how frequent the alteration of the barrier is in retinal disease. Vitreous fluorophotometry, on the other hand, is a more recent quantitative method that has opened interesting possibilities in early diagnosis of barrier alteration. It appears to be a research tool of much potential. Finally, the pathology of the blood-retinal barrier is examined with particular emphasis on the role of alterations of the barrier in the pathophysiological mechanisms of retinal disease. An attempt is made to separate the retinal pathology associated with alteration! of the inner blood-retinal barrier from that characterized by break down of the outer blood-retinal barrier. We hope this book will serve as a much needed reference source for students of the blood-retinal barriers and show the present limitations of our understanding of the basic mechanism of the blood retinal barrier in both health and disease. PREFACE vii I would like to thank especially Professors Norman Ashton and Paul Henkind who, with their experience and knowledge, helped sig nificantly in the scientific organization of the meeting. The meeting was made possible by substantial financial support from NATO. The Institute Nacional de Investigacao Cientifica of Portugal also contributed with its support to the success of the meeting. I wish to thank their representatives for their oustanding generosity and help. Jose G. Cunha-Vas LECTURERS DESMOND ARCHER Professor and Chairman, Department of Ophthalmology, the Queen's University of Belfast, Royal Victoria Hospital, Belfast, N. Ireland, U.K. ANDERS BILL Professor, Department of Physiology and Medical Biophysics Uppsala University, Uppsala, Sweden. LASZLO BITO Associate Professor, Laboratory of Ocular Physiology, Research Division, Department of Ophthalmology, Columbia University, College of Physicians and Surgeons, New York, U.S.A. MILTON BRIGHTMAN Director, Laboratory of Neuropathology and Neuroanatomical Sciences, National Institute of Neurological and Communi cative Diseases and Stroke, National Institutes of Health, Bethesda, Maryland, U.S.A. ARCELIO CARVALHO Professor and Director, Center for Cell Biology, Department of Zoology, University of Coimbra, Portugal. GABRIEL COSCAS Professor and Director, Clinique Ophtalmologique, Universite de Paris, Hopital Communale de Creteil, Paris, France. JOSE CUNHA-VAZ Professor, Department of Ophthalmology, the Abraham Lincoln School of Medicine, University of Illinois College of Medicine; Director, Retina Service, University of Illinois Eye and Ear Infirmary, Chicago, Illinois, U.S.A. Professor and Chairman, Department of Ophthalmology, University of Coimbra, Portugal. LECTURERS X AUGUST DEUTMAN Professor and Head, Department of Ophthalmology, University Of Nijmegen, Nijmegen, Netherlands. DANIEL FINKELSTEIN Associate Professor, Retinal Vascular Center, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, U.S.A, MORTON GOLDBERG Professor and Head, Department of Ophthalmology, the Abraham Lincoln School of Medicine, University of Illinois College of Medicine; Ophthalmologist-in-Chief, University of Illinois Eye and Ear Infirmary, Chicago, Illinois, U.S.A. PAUL HENKIND Professor and Chairman, Department of Ophthalmology, Albert Einstein College of Medicine; Montefiore Hospital and Medical Center; Bronx, New York, U.S.A. ABEL IAJTHA Director, Center for Neurochemistry, Rockland Research Institute, Ward's Island, New York, U.S.A. ALAN IATIES Professor, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, u.s.A. JOAO P. DE LIMA Associate Professor, Department of Physics, University of Coimbra, Portugal; Senior Researcher, Faculty of Medicine, University of Coimbra, Portugal. DAVID MAURICE Adjunct Professor of Surgery, Department of Surgery, Division of Ophthalmology, Stanford University School of Medicine, Stanford, California, U.S.A. STANLEY RAPOPORT Director, Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore City Hospitals, Baltimore, Maryland, U.S.A. MARK TSO Professor, Department of Ophthalmology, the Abraham Lincoln School of Medicine, University of Illinois College of Medicine; Director, Georgiana Theobald Ophthalmic Pathology Laboratory; Director, Macula Clinic, University of Illinois Eye and Ear Infirmary, Chicago, Illinois, U.S.A. CONTENTS PART I GENERAL ASPECTS OF MEMBRANE PERMEABILITY Structure and Function of Cell Membranes 1 P, Carvalho Biophysical Aspects of Membrane Permeability 47 J. J. P. de Lima PART II SITES AND FUNCTIONS OF THE BLOOD-BRAIN AND BLOOD-RETINAL BARRIERS Cerebral Endothelium, Blood-Brain-Barrier and the Astrocyte Membrane 65 K. Dorovini-Zis, J. J. Anders, and M. Y-1. Brightman Cerebrovascular Permeability in the Normal Brain and Following Osmotic Opening 81 S. I. Rapoport Sites and Functions of the Blood-Retinal Barriers 101 J. Cunha-Vaz PART III TRANSPORT AT THE BLOOD-BRAIN AND BLOOD-RETINAL BARRIERS Alterations of Amino Acid Transport in the Central Nervous System • • • • 119 A. Lajtha and H. Sershen Transport Functions of the Blood-Retinal Barrier System and the Microen vironment of the Retina . • • • • 133 L. Bito and C. J, deRousseau xi
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