VISUAL ADAPTATION IN THE VERTEBRATE RETINA

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A major objective of the proposed research program is to identify the subcellular basis of abnormalities that affect visual adaptation in inherited night-blinding retinal disorders. The thesis we propose to examine is that some disorders of this type are manifestations of an aberration in the processes by which the visual cell renews its molecular constituents (e.f., disc lamellae, synaptic vesicles, and other membrane-bound organelles), and that an early stage in the pathogenesis of the disease involves a disruption of the normal cytoskeletal architecture, in particular, the microtubular system. Accordingly, we propose to study with immunocytochemical and ultrastructural methods the organization of the microtubular system in photoreceptors of the cat retina, and to determine the effects on structure and synaptic transmission of the microtubule-disrupting agent, vincristine. Similar methods will be used to examine the cytoskeletal elements of visual cells in animal models of hereditary retinal disorders, namely, the night-blind Appaloosa horse, and two species of dog affected with late-onset progressive retinal atrophy (miniature poodle and Tibetan terrier). In addition, we will attempt to determine changes in rhodopsin density and visual sensitivity (and the relationship between these parameters) at various stages in the progressive disease affecting the Tibetan terrier. Because electroretinography has assumed an important role in detection of the widespread retinal dysfunction associated with hereditary retinal disease, we plan to conduct a component analysis of the ERG designed to provide information on the cellular elements that contribute to the complex waveform of the response. Lastly, intracellular studies are to be performed on isolated Muller cells from the cat retinal to determine those membrane properties that relate to the putative roles of the retinal glia in the generation of components of the ERG, and in maintaining a stable extracellular environment for neuronal function.