The described projects deal with the structure, function and metabolism of specific retinal cells involved in the processing of visual information. Our current interest is in how light and also molecules acting at surface receptors of photoreceptors modify their biochemistry and physiology. We will continue to study the kinetics of light dependent nucleotide metabolism in outer segments of amphibian photoreceptors. This project involves illuminating retinas for known brief intervals, ultrarapid-freezing of their outer segment surface, and obtaining sections of frozen outer segments for cGMP assay. The new projects concern the levels of cGMP, GTP, and GDP in OS as a function of the adaptive state of the receptor, including conditions where the medium has different buffered calcium levels.
One aim i s to help characterize the modulation of cyclase activity in the intact photoreceptor A second project focuses on membrane receptors which can modulate light-sensitive cAMP in dark adapted photoreceptors. Tryptamine, serotonin, and a purported dopamine D2 agonist, LY 17155, eliminate this pool when applied in the dark. We plan to further characterize the receptors, to localize the receptors by slide-binding autoradiography, and as a function of the diurnal cycle to quantify endogenous ligands that may regulate this cAMP pool. A third project relates to the high taurine content of photoreceptors, a molecule whose deficiency causes loss or damage of these cells, particularly cones. Hypotheses for taurine function in photoreceptors have included osmoregulation and membrane stabilization. In addition, investigations of cardiac muscle and adipose tissue have called attention to the interaction of receptors. As such hypotheses for the function of this molecule require some interaction of taurine with membrane or channel proteins, we plan to identify and characterize bovine retinal and/or photoreceptoral proteins which bind taurine, to investigate any relation to insulin receptors, with the long range aim of isolating and inserting such protein(s) in artificial membrane vesicles to help address their function. Investigations on the details of photoreceptor structure and biochemistry are particularly important in view of the many types of blindness apparently based on defects of an eventual loss of these cells.
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