Several laboratory studies indicate that the indolamine hormone melatonin, is synthesized by both the pineal gland and retina on a cyclic rhythm with peak levels during the dark period. While the role of melatonin in the retina is not well understood, many investigators have suggested that melatonin may be involved in other important diurnal events that normally occur in the retina, such as photoreceptor outer segment disc shedding and phagocytosis, photomechanical movements, and modulation of neurotransmitter release. Results of these studies, however, are very difficult to interpret without precise identification of the retinal neurons involved in various aspects of the retinal melatonin system. The goal of the proposed research is to extend our previous studies on localization of retinal melatonin-synthesizing cells and cells with which they interact, and to identify cellular sites of action of melatonin in the retina. With an understanding of the sites of melatonin synthesis and action, we can then perform well- controlled, interpretable experiments to study the mechanisms of regulation and function of melatonin in the retina. We will use specific immunochemical probes to identify the cells that possess the melatonin-synthesizing enzymes, and the cells that possess the proposed melatonin receptor. Additionally, these antibodies will be used in physiological studies to interfere with specific aspects of the melatonin system, and in double-label experiments with radioactive neurotransmitters to identify the cellular interactions with the cells of the melatonin system. For an understanding of the physiological dynamics of melatonin in the retina, identification of the retinal neurons involved in the various functions attributed to melatonin is crucial. Since melatonin may be involved in physiological processes required for normal maintenance of photoreceptors, an understanding of the mechanism of melatonin regulation and function may therefore be important for future identification of possible abnormal states of the melatonin pathway in dystrophic retinas.
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