ROLE OF DOCOSAHEXAENOIC ACID METABOLISM IN RETINA

二十二碳六烯酸的代谢及其生理意义 酸是光感受器的一种主要脂肪酸，在很大程度上仍不为人所知。 本建议是我们正在进行的研究的继续 关注二十二碳六烯酸细胞生物学的几个方面 酸代谢。需要检验的假设是，供应， 二十二碳六烯酸在视觉细胞中的摄取和代谢 在发展、更新和发挥作用方面发挥着核心作用 光感受器膜。这项提议是在出生后提出的 研究二十二碳六烯酸代谢的发展途径 外周前后分离的视杆感光细胞 正常小鼠和视网膜病变小鼠节段的生物发生 退化。由于二十二碳六烯酸是从亚麻酸中提取的 酸，一种由饮食提供的基本脂肪酸，其来源是 视网膜二十二碳六烯酸，其由亚麻酸合成 肝脏及其通过血液到视网膜的运输，将是 学习。 这项提案的另一个目标是将二十二碳六烯酸 光感受器脱落和吞噬作用的代谢 青蛙。视网膜合成二十二碳化合物(22碳，白三烯- 如化合物)。这项提议将检验这样一种假设： 代谢物参与信号传递机制，涉及 光感受器脱落。脱落后形成的类二十二碳化合物 负责产生二十二碳七烯酸的酶将是 特色化的。产生二十二碳素类化合物的可能性 与花生四烯酸相关的脂氧合酶不同 本课程将探讨酸的代谢。此外，亚细胞 二十二碳三烯的本地化生产将会确定。 为这些研究提出的方法结合了细胞生物学 技术(分离的杆状感光细胞，放射自显影 和眼杯制剂)具有高度敏感性和特异性 生化程序(高效液相色谱， 毛细管气相色谱、气相色谱-质谱法 光谱分析)，并应有助于更好地理解 二十二碳六烯酸在视觉细胞中的作用。

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.