Research is proposed to examine the cell and molecular biology of the vertebrate retina. The continuous turnover of photoreceptor outer segments is achieved by a perfect balance between the amount of new membrane added at the base of the cell, and an equivalent amount of membrane shed at the tip, thus keeping the outer segments at a constant length. One of the major goals of the proposed research is to more fully understand the underlying events involved in rod shedding. Using the frog retinas as a model system and the techniques of anatomy and biochemistry, we will examine in detail the complex process through which the apical end of the rod outer segment is induced to shed. Specifically in both in vivo and in vitro experiments, we propose to: 1) determine the link between outer segment renewal and shedding, 2) investigate the underlying molecular events in rod shedding, 3) determine the role of the pigment epithelium in rod shedding, 4) investigate indoleamine metabolism in the retina with specific emphasis on melatonin, 5) investigate catecholamine metabolism in the retina. Further experiments are included to characterize the role of neuroactive peptides in the retina, specifically somatostatin, which has been localized to a single class of interplexiform cells in the frog retina. These experiments should provide important information on the normal function of the retina, and since a disruption or imbalance in the shedding process would have pathological consequences for the photoreceptors, we may gain new information on the cause of retinal degenerations.
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