STUDIES ON DISK RENEWAL IN RETINAL VISUAL CELLS

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Photoreceptor function depends on maintenance of a delicate balance between the processes of photosensitive membrane assembly and its degradation. These processes occur in a rhythmic fashion in vertebrate retina and understanding the factors controlling rhythmicity may prove important in understanding pathological processes involving photoreceptors. Our goal is to understand the regulation of cyclic photoreceptor metabolism. The processes to be studied are rod photoreceptor disc shedding, cone retinomotor movement and rhythmic melatonin metabolism. Each process exhibits circadian rhythmicity in its activity and in the principal model used in these studies, Xenopus laevis, can be studied in detail in an in vitro preparation, accessible for experimental manipulation. A major goal is to explore the mechanisms by which "melatonin-like" copmpounds and retinal dopamine interact as signals respectively for darkness and light. Additional studies using in vitro preparations derived from Rana pipiens and from laboratory rats will be used to investigate the mechanisms by which disc shedding is triggered by light and by a circadian clock. We will analyze the properties of a circadian clock localized in the eye by monitoring circadian release of melatonin. These investigations will require the use of in vitro culture, radioimmunoassay, neuropharmacological, biochemical and electrophysiological techniques. It is expected that understanding regulation of rhythmic photoreceptor metabolism will provide a new basis for evaluating mechanisms of pathogenicity in reinal degenerative diseases.