Ординатура / Офтальмология / Английские материалы / The Retinal Muller Cell Structure and Function_Sarthy, Ripps_2001

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, Washington. 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

Figure 1.1. The four types of glial cells in the rabbit retina. A. Muller cell filled by intracellular injection with horseradish peroxidase. B. Astrocyte labeled with a monoclonal (MAI) antibody. C. An oligodendrocyted filled with biocytin extends processes that ensheathe the bundles of medullated nerve fibers that enter the optic nerve. D. lectin-labeled microglial cell shows the multiple small branches that project from the cell body (Robinson, 1992). (Copyright 1992 Today's Life Science, reprinted with permission.)

Müller cells are ubiquitous, and save for the optic nerve head, are found in all retinal regions of every vertebrate studied, including the central fovea of primates (Yamada, 1969; Distler and Dreher, 1996). In species with avascular retinas (lizards, amphibians, birds, and some mammals), Müller cells are the only glial elements that can be detected in the neural retina (Pedler, 1963; Rasmussen, 1974; Stone and Dreher, 1987; Schnitzer, 1988a).

There are between 106 and 107 Müller cells in the mammalian retina (Robinson and Dreher, 1990; Dreher et al., 1992; Reichenbach and Robinson, 1995; Distler and Dreher, 1996), and they occupy between 6–10% of the total cytoplasmic volume (Rasmussen, 1975; Reichenbach and Wohlrab, 1986). The measurements ofJeon et al. (1998) on mouse, rabbit, and monkey retinas indicate that Müller cells account for 16–22% of the cell bodies in the inner nuclear layer (INL); these data are shown in Fig. 1.3B together with comparable values for some of the other retinal cell types. However, the population density and morphology of Müller cells vary in different parts of the retina. Cells located in regions close to the ora serrata are shorter, have stouter trunks and broader endfeet, and are present in lower density (Fig. 1.4) than in more central locations (Uga, 1974; Rasmussen, 1974,1975; Dreher et al., 1988; Gaur et al., 1988; Reichenbach et al., 1989; Robinson and Dreher, 1990). In the far periphery of monkey retina, for example, cell density is about 6,000/mm2, whereas in the parafoveal region, the Müller cells have long slender trunks and reach a peak density of more than 30,000/mm2 (Distler and Dreher, 1996). The extreme variability in these morphometric parameters undoubtedly reflects the functional requirements of different retinal regions, and the special properties of the microenvironment in which the cells develop (Reichenbach et al., 1989).

Regional differences aside, Müller cells of all species have many common features. At the ultrastructural level (Fig. 1.5), the Müller cell cytoplasm appears more electron dense than neighboring neurons, and contains a well-developed endoplasmic reticulum and varying amounts of glycogen granules (Hogan et al., 1971; Uga, 1974). The cell nuclei are typically oval or polygonal and are generally located in the middle of the INL.

Mitochondria are located throughout the Müller cell cytoplasm, and in some retinas they may be found concentrated toward one end of the cell (cf. Uga and Smelser, 1973b; Rasmussen, 1974). It has been suggested that the location of the mitochondria within the Müller cell relates to the energy requirements of its neuronal neighbors (Rasmussen, 1973), but this seems unlikely. For example, mitochondrial density is often highest near the external limiting membrane in a region bordering the photoreceptor inner segments (Uga and Smelser, 1973a; Rasmussen, 1975); this area of the visual cell contains one of the highest concentrations of mitochondria of any body tissue. Recently, studies of mitochondrial migration and localization in

4 CHAPTER 1

intact and isolated mammalian Müller cells provided evidence that the distribution of these organelles is determined by the local cytoplasmic oxygen pressure. Clustering occurs in regions where the Po2 levels exceed ~10-20 mmHg (Germer et al., 1998a, b), but the mechanism underlying mitochondrial migration, and the functional implications of this observation remain to be determined.

1.1.1. Relation to Neurons

As already mentioned, the intimate association between Müller cell processes and retinal neurons implies a close functional relationship between the two cell types. In this connection, an interesting concept put forward by Reichenbach et al. (1993) suggests that cooperativity exists among cells that arise from a common stem cell to form a columnar array (cf. Chapter 2, the developmental studies by Turner and Cepko, 1987 and Turner, Snyder and Cepko, 1990). The basic tenet of this hypothesis is that one Müller cell subserves many of the metabolic, ionic, and extracellular buffering requirements of those neurons with which it shares a common progenitor (Fig. 1.6).

The idea of a functional unit in which local interactions occur between a group of retinal neurons and their supportive glial cell is an attractive concept. On this view, Müller cells need not interact with each other to accommodate the far greater number of retinal neurons they subserve. By limiting its sphere of influence, each Müller cell may only have to meet the requirements of its immediate neuronal neighbors, e.g., to maintain a stable extracellular environment in the face of intense neural activity (cf. Chapters 4 and 5). Cooperativity and intercellular communication between Müller cells and retinal neurons will be considered further in Chapters 3 and 4.

Figure 1.2. A. Light micrograph of the mudpuppy retina shows two Müller cells extending from the internal limiting membrane (ilm) to the outer limiting membrane (olm), and their relationship to the nuclear and plexiform layers of the retina. R, receptors; ONL, outer nuclear layer; OPL, outerplexiform layer; INL, inner nuclear layer; IPL, inner plexiform layer; GCL, ganglion cell layer (Dowling, 1987). (Copyright 1987Belknap Press, reprinted with permission. After Dowling [1970]. Copyright 1970 Association for Research in Vision and Ophthalmology, reprinted with permission.) B. Schematic drawing of mammalian Müller cell perikarya and their processes interdigitating with every class of retinal neuron; the figure was reconstructed from electron micrographs of the human retina. Shown are the photoreceptors (P) of the outer nuclear layer, the horizontal (H), bipolar (B), and amacrine (A) cells of the inner nuclear layer, and the ganglion cells (G) whose axons form the nerve fiber layer. Note the location of the oval-shaped, densely stained Müller cell nuclei near the innermost part of the INL. Intercellular junctions can be seen at the outer limiting membrane, distal to which villous processes (p) embrace the myoid region of the photoreceptor. Müller cells abut the internal limiting membrane at the vitreal border, where they terminate in pyramidal-shaped endfeet (Hogan et al., 1971). (Copyright 1971 W.B. Saunders Co., reprinted with permission.)