The Retina: A Model for Cell Biology Studies

369 Pages·1986·26.177 MB·English

by  Ruben Adler (Eds.)

CELLULAR NEUROBIOLOGY: A SERIES
EDITED BY SERGEY FEDOROFF
THE NODE OF RANVIER
Edited by JOY C. ZAGOREN AND SERGEY FEDOROFF
THE RETINA: A MODEL FOR CELL BIOLOGY STUDIES, PART I
Edited by RUBEN ADLER AND DEBORA FARBER
THE RETINA: A MODEL FOR CELL BIOLOGY STUDIES, PART II
Edited by RUBEN ADLER AND DEBORA FARBER
THE RETINA
A Model for Cell Biology Studies
Part I
EDITED BY
RUBEN ADLER DEBORA FARBER
The Michael M. Wynn Center for the Jules Stein Eye Institute
Study of Retinal Degenerations UCLA School of Medicine
The Wilmer Ophthalmological Institute Los Angeles, California
The Johns Hopkins University
School of Medicine
Baltimore, Maryland
1986
< $>
ACADEMIC PRESS, INC.
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COPYRIGHT © 1986 BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED.
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ACADEMIC PRESS, INC.
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ACADEMIC PRESS INC. (LONDON) LTD.
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Library of Congress Cataloging in Publication Data
Main entry under title:
The Retina : a model for cell biology studies.
Includes bibliographies and index.
1. Retina-Cytology. I. Adler, Ruben. II. Farber,
Debora. [DNLM: 1. Retina-cytology. 2. Retina-
physiology. WW 270 R43804]
QP479.R468 1986 599\01823 85-23005
ISBN 0-12-044275-2 (Pt. I : alk. paper)
PRINTHD IN THH UNITHD STATUS OF AMHRICA
86 87 88 89 9 8 7 6 5 4 3 2 1
This book is dedicated to
Alfred J. ("Chris") Coulombre,
a pioneer of the field of retinal cell biology
and an outstanding human being
CONTRIBUTORS
Numbers in parentheses indicate the pages on which the authors' contributions
begin.
Ruben Adler (1, 111), The Michael M. Wynn Center for the Study of Retinal
Degenerations, The Wilmer Ophthalmological Institute, The Johns Hopkins
University, School of Medicine, Baltimore, Maryland 21205
Joseph C. Besharse (297), Department of Anatomy and Cell Biology, Emory
University School of Medicine, Atlanta, Georgia 30322
Beth Burnside (151), Department of Physiology-Anatomy, University of Cal-
ifornia, Berkeley, Berkeley, California 94720
Allen Dearry (151), Department of Physiology-Anatomy, University of Cal-
ifornia, Berkeley, Berkeley, California 94720
Debora B. Farber (1, 239), Jules Stein Eye Institute, UCLA School of Medi-
cine, Los Angeles, California 90024
Christopher C. Getch (67), Department of Biology, Princeton University,
Princeton, New Jersey 08544
Paul A. Hargrave (207), Department of Ophthalmology and Department of
Biochemistry and Molecular Biology, College of Medicine, University of Flor-
ida, Gainesville, Florida 32610
Robert E. Marc (17), Sensory Sciences Center, University of Texas Graduate
School of Biomedical Sciences, Houston, Texas 77030
Terrence A. Shuster (239), Jules Stein Eye Institute, UCLA School of Medi-
cine, Los Angeles, California 90024
Malcolm S. Steinberg (67), Department of Biology, Princeton University,
Princeton, New Jersey 08544
xi
PREFACE
Retinal Cell Biology: Past, Present, and Future
It is difficult at times to define the field of cell biology. One need only attend
the annual meeting of the American Society for Cell Biology to experience the
enormous breadth of this field. Nonetheless, many would define cell biology in a
very general way as a combination of microscopic anatomy, biochemistry, phys-
iology, and pathology.
The confluence of these disciplines into a unifying field did not really occur
until the 1950s, but we can trace the ancestry of the discipline to Matthias
Schleiden, Theodor Schwann, and Rudolf Virchow, the botanist, histologist, and
pathologist, respectively, who are generally credited with the development of the
cell theory in 1839. Somewhat later in that century the study of retinal cells was
initiated. Ultimately, Max Schultze (1867) set forth the duplicity theory for
photoreceptor function through his observation that cones are the receptors for
bright light and color and that rods function in dim light. Subsequently Franz
Boll (1877) observed that the photochemical event underlying light detection was
the bleaching of ' 'visual purple" now known as rhodopsin. He also suggested
that a carotenoid might be a precursor for this photopigment. His contemporary,
Willy Kuhne (1878) was the first to solubilize photopigments in bile salts thereby
demonstrating their hydrophobic nature. Santiago Ramon y Cajal (1894) soon
thereafter modified methods shared by fellow Nobel laureate Camillo Golgi and
displayed the neuronal network of the retina in such breathtaking detail that his
work serves as the standard even to this day. Therefore, by the turn of the
century, the study of retinal cells by representatives of the separate disciplines of
microscopic anatomy, biochemistry, and physiology was well established.
Retinal research was graced by investigators of equivalent intuition and
creativity during the first half of this century. The disciplines of electrophysiolo-
gy and biochemistry, exemplified by Ragnar Granit, Haldane Hartline, and
George Wald, produced insights into retinal electrical activity, cell interactions,
and photochemistry worthy of the Nobel Prize so appropriately bestowed upon
them. The contributions of these gifted scientists and their contemporaries drew
xiii
XIV PREFACE
into the field a new generation of capable scientists armed with new and powerful
techniques. Fritiof Sjostrand, Eichi Yamada, Adolph Cohen, Brian Boycott,
John Dowling, and many others began the systematic examination of retinal cells
by electron microscopy. The application of tissue autoradiographic technique to
retinal studies by Richard Sidman, Richard Young, and Bernard Droz in the
early to mid 1960s added a dynamic component to microscopy. It was possible
for the first time to mark retinal birth dates and to study the metabolism of
individual cell types.
Particularly suitable for autoradiographic studies were the photoreceptors with
their highly compartmentalized structure and their prodigious biosynthesis and
assembly of membranes. By virtue of this technique, an entirely new role was
discovered for retinal pigment epithelial cells, the phagocytosis and photorecep-
tor outer segment membranes. Furthermore, a new research strategy began to
emerge. Whereas scientists of the past had adhered rather strictly to their chosen
disciplines each of which drew upon a rather limited constellation of methods,
the new approach was to combine the methods of multiple disciplines in order to
address problems of ever-increasing complexity. This is the essence of cell
biology and, with the advent of this approach, retinal cell biology came into full
bloom.
A subject that benefited greatly from this philosophy was the study of mem-
brane biosynthesis in photoreceptors. Michael Hall and I combined radio-
biochemical and autoradiographic methods in the study of rhodopsin bio-
synthesis and assembly into outer segment disk membranes, and David
Papermaster and Barbara Schneider applied high-resolution immunocytochemi-
cal methods to plot membrane trafficking from sites of synthesis to sites of
assembly within the cell.
Another area that was aided tremendously by this combined approach was that
of retinal neurotransmitter studies. Relatively little progress was made on this
subject until the introduction of autoradiographic and immunocytochemical tech-
niques. Autoradiographic analysis of high-affinity-uptake sites for neurotrans-
mitters as initiated by Berndt Ehinger and Dominic Lam combined with immu-
nocytochemical localization of enzymes involved in neurotransmitter synthesis
have been very illuminating as have studies introduced by Harvey Karten and
Nicholas Brecha on the localization of the myriad of peptides that are now known
to exist either as neurotransmitters or neuromodulators in the amacrine cells of
the retina. Immunocytochemical techniques are now employed by a growing
number of retinal cell biologists and, when applied at high resolution in particu-
lar, will add significantly to our understanding of the molecular division of labor
among retinal organelles.
Research during the 1970s has featured another group of exciting topics. The
subject of photoreceptor transduction has been hotly debated among proponents
who favor the hypothesis that calcium serves as the internal messenger during
PREFACE xv
signal amplification, as first proposed by William Hagins and Shuko Yoshikami,
and the adherents of cyclic guanosine monophosphate, as initially suggested
from the work of Mark Bitensky and collaborators. Whatever the outcome, it
appears likely that the photoreceptors will be the first sensory cells in which the
mystery of transduction is solved. Furthermore, the contributions of Debora
Farber and Richard Lolley and their collaborators have shown how cyclic nu-
cleotide metabolism, when perturbed, can lead to photoreceptor degeneration of
the type observed in some animal models for retinitis pigmentosa.
Rhythmic phenomena in the retina, pioneered by Matthew LaVail through his
observations on cyclic outer segment disk shedding, have also been a subject of
intense investigation resulting in the discovery by several laboratories that these
activities are controlled intraocularly rather than by remote tissues such as the
pineal gland. The development of an in vitro preparation by Joseph Besharse for
the study of the molecular basis of rhythmic activity has already moved us
significantly toward an understanding of these processes. Superimposed upon
these metabolic studies has been exciting progress in our understanding of the
role of extracellular adhesion and matrix molecules in retinal development and
trophic interactions. The recent work of Ruben Adler and associates now pro-
vides us with the capability to study the differentiation of photoreceptors in
culture.
Another informational leap is now occurring in retinal cell biology, spawned
by the technology that has impacted so favorably on other tissues as well,
namely, recombinant DNA research. Some of the most exciting observations are
so new that they have not yet appeared in print. The first application of recombi-
nant DNA methods to retinal research has involved the amino acid sequencing of
proteins involved in phototransduction. The sequencing of bovine rhodopsin by
conventional methods was initiated by Paul Hargrave and his colleagues shortly
after this protein was purified by Joram Heller in 1968.
About 15 years of intensive work were required before the primary structure of
this hydrophobic membrane protein was solved. Utilizing this important se-
quence information, the fact that the vertebrate photopigments are well con-
served, and rapid nucleotide sequencing developed independently by the labora-
tories of Frederick Sanger and Walter Gilbert, Jeremy Nathans and David
Hogness have sequenced human rhodopsin and all of the human cone opsins in
the space of just a few years. Additionally, the primary sequences of all of the
subunits of the G protein and light-activated cyclic nucleotide phosphodiesterase
thought to be involved in phototransduction will probably be solved in several
laboratories by the time that these books (Parts I and II) appear in print. With this
information in hand we will have, for the first time, the opportunity to determine
the molecular basis of several forms of inherited photoreceptor degeneration that
are thought to involve one or more of these proteins.
We are currently experiencing a fast-moving and exciting period for the retinal
XVI PREFACE
cell biologist and the opportunities appear almost limitless at this time. It is
therefore most fitting that a two-part series entitled The Retina: A Model for Cell
Biology Studies should be made available to those who already have an interest in
this subject and to others who may be inspired to join us. We hope that you find
the subject as inviting and rewarding as we have during the past two decades.
DEAN BOK
THE RETINA, PART I
ISSUES AND QUESTIONS IN CELL BIOLOGY
OF THE RETINA
DEBORA FARBER
Jules Stein Eye Institute
UCLA School of Medicine
Los Angeles, California
RUBEN ADLER
The Michael M. Wynn Center for the
Study of Retinal Degenerations
The Wilmer Ophthalmological Institute
The Johns Hopkins University
School of Medicine
Baltimore, Maryland
I. Introduction 2
II. The Adult Retina 3
A. Localization within the Eye 3
B. Cell Layers and Neuronal Networks 4
C. Glia 8
III. The Developing Retina 9
IV. The Pathological Retina 14
V. Concluding Remarks 15
References 16
Most investigations of enzymes and other chemical constituents of the developing chick
retina are of recent date. . . . thus far inadequate attention has been given to chemical dif-
ferences between the pigmented epithelium and the neural retina. ... it seemed reasonable to
trace in more detail the histogenesis of this tissue and to make correlation of the findings with
the data on retinal chemistry. [Coulombre, 1955]
1
Copyright © 1986 by Academic Press, Inc.
All rights of reproduction in any form reserved.