Convincing evidence exists for the presence in retina of a cellular/biochemical system that synthesizes and secretes methoxyindoles, such as melatonin. The synthesis of these compounds is regulated by photoperiod, and evidence is presented for a role of methoxyindoles in rhythmic metabolism in the photoreceptor-pigment epithelial complex. The goal of the proposed research is to characterize the methoxyindole system of retina. To this end, the retinal cell type(s) that synthesize methoxyindoles will be localized using immunohistochemical and biochemical techniques, and the molecular mechanisms involved in the regulation of methoxyindole biosynthesis and release will be investigated. Methoxyindole receptors in retina and pigment epithelium-choroid will be characterized using radioligand binding methodologies, and localized by autoradiography. In addition, the possible involvement of the methoxyindoles in synaptic neurotransmission and the role of these compounds in the regulation of photoreceptor disc shedding will be investigated. The research is significant because it will thoroughly characterize a cellular/biochemical system that may play an important role in retinal physiology. Due to the high probability that these compounds play a vital role in photoreceptor outer segment turnover, an understanding of this system may contribute to our understanding of visual cell physiology and perhaps in our understanding of pathological processes which result in photoreceptor degeneration.
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