The metabolism and physiological significance of docosahexaenoic acid, a major fatty acid of photoreceptors, remain largely unknown. The present proposal is a continuation of our ongoing studies focusing on several aspects of the cell biology of docosahexaenoic acid metabolism. The hypothesis to be tested is that the supply, uptake and metabolism of docosahexaenoic acid in the visual cell plays a central role in the development, renewal and function of photoreceptor membranes. The proposal follows a postnatal developmental approach to study docosahexaenoic acid metabolism in dissociated rod photoreceptor cells prior, during and after outer segment biogenesis in normal mice and in mice with retinal degeneration. Since docosahexaenoic acid is derived from linolenic acid, an essential fatty acid supplied by the diet, the origin of retinal docosahexaenoic acid, its synthesis from linolenic acid in the liver and its transport via the blood to the retina, will be studied. Another goal of this proposal is to correlate docosahexaenoic acid metabolism with photoreceptor shedding and phagocytosis in the frog. The retina synthesizes docosanoids (22-carbon, leukotriene- like compounds). This proposal will test the hypothesis that these metabolites are involved in signaling mechanisms involved in photoreceptor shedding. Docosanoids formed in response to shedding and the enzymes responsible for docosanoid production will be characterized. The possibility that the docosanoid-producing enzymes are distinct from lipoxygenases involved in arachidonic acid metabolism will be explored. In addition, the subcellular localization of docosanold production will be determined. The approach proposed for these studies combines cell biological techniques (dissociated rod photoreceptor cells, autoradiography and eye cup preparations) with highly sensitive and specific biochemical procedures (high-performance liquid chromatography, capillary gas-liquid chromatography, gas chromatography-mass spectrometry) and should contribute to a better understanding of the role of docosahexaenoic acid in visual cells.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Louisiana State University Hsc New Orleans
Schools of Medicine
New Orleans
United States
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Santos, F F; de Turco, E B; Gordon, W C et al. (1995) Alterations in rabbit retina lipid metabolism induced by detachment. Decreased incorporation of [3H]DHA into phospholipids. Int Ophthalmol 19:149-59
Rodriguez de Turco, E B; Gordon, W C; Bazan, N G (1994) Docosahexaenoic acid is taken up by the inner segment of frog photoreceptors leading to an active synthesis of docosahexaenoyl-inositol lipids: similarities in metabolism in vivo and in vitro. Curr Eye Res 13:21-8
Bazan, N G; Rodriguez de Turco, E B (1994) Review: pharmacological manipulation of docosahexaenoic-phospholipid biosynthesis in photoreceptor cells: implications in retinal degeneration. J Ocul Pharmacol 10:591-604
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Gordon, W C; Rodriguez de Turco, E B; Bazan, N G (1992) Retinal pigment epithelial cells play a central role in the conservation of docosahexaenoic acid by photoreceptor cells after shedding and phagocytosis. Curr Eye Res 11:73-83
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Rodriguez de Turco, E B; Gordon, W C; Peyman, G A et al. (1990) Preferential uptake and metabolism of docosahexaenoic acid in membrane phospholipids from rod and cone photoreceptor cells of human and monkey retinas. J Neurosci Res 27:522-32
Bazan, N G; Scott, B L (1990) Dietary omega-3 fatty acids and accumulation of docosahexaenoic acid in rod photoreceptor cells of the retina and at synapses. Ups J Med Sci Suppl 48:97-107

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