The research proposed in this application is directed at understanding the mechanism through which specific degenerative diseases act to alter retinal metabolism. We will exploit a novel culture preparation which allows both morphological and biochemical analysis to be performed on small retinal buttons from human eyes. We will elevate the levels of cyclic nucleotides or ornithine concentrations in the culture medium to stimulate metabolite imbalance in the disease state. By utilizing the appropriate labeled precursor we will follow the changes in specific molecular components with biochemical techniques and identify the cell type in which these changes take place with autoradiography. Renewal pattern of RNA, protein and lipids will be evaluated with this systematic approach. We will determine how renewal processes in the retina are altered when imbalances in specific metabolites occur and provide fundamental information regarding the mechanism through which degenerative changes are manifest in the human retina.
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