The Retinal Muller Cell: Structure and Function PDF
Preview The Retinal Muller Cell: Structure and Function
The Retinal Müller Cell PERSPECTIVESINVISIONRESEARCH Series Editor: Colin Blakemore University of Oxford Oxford, England Biochemistry of the Eye ElaineR.Berman Development of the Vertebrate Retina Edited by Barbara L. Finlay and Dale R. Sengelaub ParallelProcessingintheVisualSystem THECLASSIFICATIONOFRETINALGANGLIONCELLSANDITSIMPACTON THENEUROBIOLOGYOFVISION Jonathan Stone Presbyopia Research FROM MOLECULAR BIOLOGY TO VISUAL ADAPTATION Editedby Gérard Obrechtand LawrenceW. Stark The Retinal Müller Cell STRUCTUREANDFUNCTION Vijay Sarthy and Harris Ripps Visual Development Nigel W. Daw A Continuation Order Plan is available for this series. A continuation order will bring delivery of each new volume immediately upon publication. Volumes are billed only upon actual shipment. For further information please contact the publisher. The Retinal Müller Cell Structure and Function Vijay Sarthy Northwestern University Medical School Chicago,Illinois and Harris Ripps UniversityofIllinoisCollegeofMedicine Chicago,Illinois Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow eBookISBN: 0-306-46841-7 Print ISBN: 0-306-46470-5 ©2002 Kluwer Academic Publishers New York, Boston, Dordrecht, London, Moscow All rights reserved No part of this eBook may be reproduced or transmitted in any form or by any means, electronic, mechanical, recording, or otherwise, without written consent from the Publisher Created in the United States of America Visit Kluwer Online at: http://www.kluweronline.com and Kluwer's eBookstore at: http://www.ebooks.kluweronline.com To Mary andJeanne Preface The human brain contains more than a billion neurons which interconnect to form networks that process, store, and recall sensory information. These neuronal activities are supported by a group of accessory brain cells collec- tively known as neuroglia. Surprisingly, glial cells are ten times more nu- merous than neurons, and occupy more than half the brain volume (Hydén, 1961). Although long considered a passive, albeit necessary, component of the nervous system, many interesting and unusual functional properties of glial cells are only now being brought to light. As a result, the status of these cellular elements is approaching parity with nerve cells as a subject for experimental study. The term glia (or glue) seems today to be a misnomer in view of the diverse functions attributed to glial cells. Experimental studies in the last three decades have clearly established that the behavior of glial cells is far from passive, and thatthey are atleastas complex as neuronswith regard to their membrane properties. In addition, glial cells are of importance in signal processing, cellular metabolism, nervous system development, and the pathophysiology of neurological diseases. The Müller cell of the verte- brate retina provides a splendid example of an accessory cell that exhibits features illustrating every aspect of the complex behavior now associated with glial cells. HISTORICAL PERSPECTIVE It was more than a century ago that the generic term neuroglia was given to the non-neuronal elements of the nervous system. The notion that neural elements are embedded in an unusual connective tissue-like matrix (Binde- gewebe) can be traced to the early writings of the eminent German patholo- gist Rudolph Virchow (1846), but the concept of neuroglia (Nervenkitt) and a description of its histological form did not appear until ten years later (Virchow, 1856; for a historical review, see Somjen, 1988). Without detract- ing from Virchow’s enormous prescience, it is worth noting that five years earlier Heinrich Müller (1851), having studied a variety of species, provided vii viii PREFACE a detailed description of the radial fibers which we now know to be the principal glial cell of the vertebrate retina. (The text of Müller’s landmark paper, together with a translation, is provided in the Appendix.) Shortly thereafter, Kolliker (1854) observed similar structures in the human retina and ascribed to them eponymously the name by which they have come to be known: the Müller cells. It is also interesting to note that whereas glial cells of the central ner- vous system (CNS) have been classified into a number of subtypes based on such distinguishing features as morphology, antigenicity, and functional properties (Raff, 1989), Müller cells are usually treated as belonging to a unique but functionally uniform class of glial cell. This is clearly not the case. Depending upon the species, there is a striking heterogeneity in Müller cell structure, antigenic properties, and responses to neurotransmit- ters. However, the molecular determinants of these differences are often unknown, and no rational basis for subclassification of Müller cells has emerged. The observed differences between species may reflect the differ- ent metabolic or functional demands on these cells, or the influence of different environmental factors; a comparative study of Müller cells from this perspective is sorely needed. In focusing on the Müller cell, we cannot ignore the wealth of informa- tion available from the study of glial cells in other regions of the CNS. Indeed, many of the defining characteristics of Müller cells, such as their electrical properties, immunochemical features, metabolic activities, and cytoplasmic content, display similarities to those found in protoplasmic astrocytes (Kettenman and Ransom, 1995). Nevertheless, the Müller cell has become highly adapted in form and function to its retinal environment, and there is little to be gained by attempting to force it into one or another of the conventional categories of neuroglia. SCOPE OF THE BOOK Chapter 1 introduces the glial cells of the retina and describes their structural features and intercellular relationships. The morphology of Müller cells is considered in detail, with special attention paid to junctional con- tacts, membrane characteristics, and other cytological features. Chapter 2 deals with the role of Müller cells in retinal development and also with features of Müller cell development itself. The lineage, birth, and deter- mination of Müller cells are reviewed. Potential roles of Müller cells in neuronal development are also discussed. Chapter 3 looks at the metabolic interactions between Müller cells and retinal neurons. The involvement of Müller cells in energy metabolism, transmitter inactivation, pH regulation, PREFACE ix and retinoid metabolism are discussed. Chapter 4 focuses on the signaling pathways between retinal neurons and Müller cells. The properties of neu- rotransmitter transporters and receptors on Müller cells are described. Chapter 5 discusses ionic properties of the Müller cell membranes, the role of Müller cells in potassium homeostasis, and the involvement of Müller cells in generating electroretinographic (ERG) potentials. Last, Chapter 6 presents an overview of the involvement of Müller cells in retinal pathology. This chapter describes putative roles of Müller cells in excitotoxicity, reac- tive gliosis, and retinal diseases. It will be clear from the information presented in these chapters that Müller cells perform a variety of tasks in the retina. Perhaps their best understood functions are in potassium homeostasis and in neurotransmit- ter uptake and metabolism. These activities support a number of vital processes in the normal retina. Müller cells play an active role in patholog- ical conditions as well. For instance, in ischemic retina, Müller cells are likely to alleviate glutamate excitotoxicity by removing excess extracellular glutamate. The strong gliotic response of Müller cells also suggests a role in the phagocytosis of cell debris and scar formation. Moreover, it has recently been discovered that reactive Müller cells produce neuroprotective cyto- kines and neurotrophic factors that alleviate neuronal damage and degen- eration. In contrast, our current knowledge of the mechanisms that deter- mine Müller cell fate and the roles of Müller cells in retinal development is still in its infancy. In writing this book, we have attempted to survey the current status of our knowledge of Müller cell structure and function with the hope that this effort will point out areas of Müller cell biology that need to be addressed in the future. Because of space constraints, we have been selective in our choice of topics and illustrations. Many similar or related examples have not been presented, and we apologize if we overlooked any important studies. Clearly, the content and emphasis of the book reflects our personal view of Müller cell biology. Although many details are still lacking, it is evident now that Müller cells and retinal neurons have evolved together to fashion an intricate cellular network, the retina, whose ultimate goal is to present a clear view of the surrounding world. ACKNOWLEDGMENTS We gratefully acknowledge the generosity of our colleagues who pro- vided illustrations and data from their published work, and the publishers who very graciously permitted us to reproduce figures. We are especially thankful to Paul Witkovsky, Jack Saari, Tom Reh, Don Puro, Lee Jampol, x PREFACE Steve Fisher, and Ruben Adler for helpful comments and suggestions on individual chapters. This book could not have been completed without the enthusiastic assistance of Jane Zakevicius, Mary Winneke of the UIC library, and the library staffs of the Marine Biological Laboratory, Woods Hole, Massachusetts, and Friday Harbor Laboratory, Friday Harbor, Wash- ington. We are grateful to Lisa Birmingham who meticulously prepared all the illustrations, and we thank Tom Porter, Michael Schütte, Etha Schuette, and Rolf Behrmann for undertaking the challenging task of translating Müller’s original report. Contents 1. Structural Organization of Retinal Glia ...................... 1 1.1. Müller Cells ......................................... 1 1.1.1. Relation toNeurons ............................ 5 1.1.2. IntercellularJunctions........................... 9 1.1.3. Müller CellsasInsulators........................ 13 1.1.4. The Zonula Adherens of the Outer Limiting Membrane..................................... 14 1.1.5. TheConfines of the SubretinalSpace ............. 17 1.1.6. TheBlood–RetinaBarrier ....................... 18 1.1.7. TheInternal LimitingMembrane ................. 22 1.1.8. Cytoskeleton ................................... 24 1.1.9. OrthogonalArrays .............................. 26 1.2.Astrocytes andMicroglia .............................. 28 1.2.1. Astrocytes...................................... 28 1.2.2. Microglia ...................................... 33 2. Role inRetinal Development .............................. 35 2.1. Lineage,Birthdate,andDevelopment of Müller Cells ..... 36 2.1.1. Lineage Relationship between Müller Cells and RetinalNeurons ................................ 36 2.1.2. Lineage Relationship with Astrocytes and Microglia 38 2.1.3. TheBirth of Müller Cells ........................ 39 2.1.4. MüllerCellDetermination ....................... 42 2.2. Roles inRetinalDevelopment .......................... 47 2.2.1. Neuronal Migration and Retinal Histogenesis ...... 48 2.2.2. ExtrinsicMolecules inRetinal Development ....... 51 2.2.3. CellAdhesionReceptors ......................... 52 2.2.4. ExtracellularMatrixMolecules andIntegrins ....... 56 ................ 2.2.5. Growth andNeurotrophicFactors 57 2.2.6. RetinoicAcid .................................. 60 2.3. Developmental Regulationof GeneExpression ......... .. 61 xi
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