Our research is directed toward developing at the molecular level an insight into the biochemistry of the visual process, and in particular how retinoids (vitamine A compounds) are stored, mobilized, transported, isomerized and utilized in the eye. We are also interested in the transport of these and other hydrophobic compounds, such as vitamin E, in the pigment epithelium and interphotoreceptor matrix and we are interested in those properties of the interphotoreceptor matrix that may affect the passage of these substances between the RPE and the retina. We will extend our studies on nutritional deficiencies, and on hereditary and acquired retinal degenerations in animals. We will also continue and expand our work on normal human eyes, so providing a reliable backdrop against which to evaluated our findings on human eyes with retinal degenerations. The distribution and isomerization of retinoids in vivo and in vitro during various stages of the visual cycle will be examined using animals on normal diets and animals on vitamin A-deficient diets supplemented with retinoic acid and pulsed with [3H]-retinoids. The properties of the interphotoreceptor matrix will be examined. This includes a study of the proteoglycans, their state of aggregation and the possible presence of free glycosaminoglycans as a result of proteoglycan degradation. We will also study the glycoproteins of the IPM, and will continue to characterize and study the high Mr glycoprotein that binds retinol and alpha-tocopherol. We will study the pigment epithelium, its role insynthesizing interphotoreceptor matrix and its role in interconverting, isomerizing, transporting and regulating the delivery of retinoids to the retina. We will use the above approaches to study retinal degenerations in animals, both hereditary (Wag-Rij and RCS rats) and acquired (zinc and vitamin A deficiencies). We will also use these approaches to study tissue from human eyes with acquired and hereditary degenerations, including retinitis pigmentosa.
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