RELATED MOLECULAR AND PHYSIOLOGICAL EVENTS IN VISION

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The overall goal of the research program is to study the chemical reactions and physiological functions of the photoreceptor, with a present emphasis on the metabolism of vertebrate photoreceptors. The metabolic reactions of a cell directly provide ATP, especially important to photoreceptors for the operation of primary active transport systems and for the phosphorylation of certain components such as rhodopsin and intermediates of the phosphatidylinositol cycle. They indirectly provide GTP, required for the very active synthesis of cGMP and the control of G- proteins. Metabolic reactions also affect the concentration of nicotinamide coenzymes (NAD+,NADP+/NADH,NADPH), compounds that are important in the rhodopsin cycle for the reduction of retinal and the oxidation of retinol. One area of investigation involves identification of the reaction(s) or components that regulate metabolic rates in vertebrate photoreceptors. For example, our initial data suggest that phosphofructokinase, an enzyme within glycolysis, mediates respiratory responses to light. A second area of study is the metabolic effects of typical physiological condtions such as darkness, various levels of illunination, and concentrations of metabolic substrates (such as glucose) or effectors (such as calcium). Using mammalian retinas we wish to determine how these conditions affect metabolic rates, concentrations of high energy nucleotides and nucleotide coenzymes, and, in turn, how these affect the ability of photoreceptors to maintain their ion concentrations, electrophysiological responses, rhodopsin cycle and structural integrity. We have already shown that the metabolic rate changes that occur under certain conditions (such as bleaching levels of 10%) are inadequate to maintain ATP and GTP concentrations. We have also observed that rhodopsin regeneration is reduced at bleaching levels above 4% and eliminated in the presence of certain glycolytic inhibitors. A third area of investigation is whether abnormalities in photoreceptor metabolism accompany specific endocrine (e.g., diabetes) or retina (e.g., degenerative) disorders. Information on mammalian photoreceptor metabolism under many circumstances may provide a basis from which clinical problems can be defined and treated. Our final area of investigation is the relationship between photorecptor components and reactions, and the electrophysiological properties of the photorecptor.