BIOCHEMISTRY OF THE RETINA & PIGMENT EPITHELIUM

视网膜的生物化学

• 批准号: 2888086
• 负责人: JOHN C SAARI
• 金额: $ 36.08万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888086
• 关键词: acyltransferase; aldehyde dehydrogenases; amacrine cells; animal tissue; biochemistry; enzyme complex; enzyme mechanism; enzyme structure; enzyme substrate; laboratory mouse; nucleic acid probes; protein structure function; retinal pigment epithelium; retinaldehyde; retinoate; retinoid binding proteins; tissue /cell culture; visual photoreceptor; visual phototransduction; vitamin metabolism

The long-term goal of this research project is to provide new molecular information about components and reactions of the visual cycle and about the control of retinoic acid biosynthesis in retina. During daylight, a continual rain of photons bleaches visual pigments in photoreceptor cells of our retinas to initiate phototransduction. Simultaneously reactions of the visual cycle in RPE replenish the bleached chromophore and provide for continual regeneration of visual pigments. Vision requires a balance between these two processes to establish a new steady level of bleached visual pigment at each different level of illumination. While phototransduction has been well studied, we know relatively little in a molecular sense of the components or control of the visual cycle. During the course of this project a detailed investigation of the enzymology and chemistry of visual cycle reactions will be carried out. Particular emphasis will be placed on determining the factors that control levels of all-trans-retinaldehyde in the photoreceptor cell, on determining the role of retinoid-binding proteins in cycle activity and on obtaining structural information about one of the enzymes of the cycle. Retinoic acid and its carrier protein CRABP are present in retina in relatively large amounts. Since this retinoid cannot be reduced to retinaldehyde or retinol in vivo, and thus cannot participate n the visual cycle, it is likely to be involved in other aspects of vitamin A function. The question of retinoic acid function in retina will be addressed, concentrating on providing a molecular description of the enzymes and control involved in its synthesis. An understanding of the underlying causes of clinical retinal disease requires an appreciation of the fundamental processes that produce the visual response. At present, the relative paucity of detailed information about visual cycle enzymes and their control and retinoic acid function and biosynthesis in retina, precludes even asking relevant questions about possible relationships to retinal disease. The concepts, structural information, antibodies, and cDNA probes that will be obtained during this project period will allow future exploration of the relationship of retinoid metabolism to retinal disease.

这一研究项目的长期目标是提供新的分子 关于视觉周期的成分和反应的信息，以及关于 视网膜中维甲酸生物合成的控制。 在白天，持续不断的光子雨使视觉色素漂白。 我们视网膜的光感受器细胞启动光传导。 视网膜色素上皮的视觉周期反应同时补充漂白的视网膜 生色团，并提供视觉色素的持续再生。 愿景需要在这两个过程之间取得平衡，以建立新的 在每个不同水平的漂白视觉色素的稳定水平 照明。虽然光传导已经被很好地研究了，但我们知道 在分子意义上相对较少的成分或控制 视觉循环。在这个项目的过程中，进行了详细的调查 将进行视觉循环反应的酶学和化学的 出去。将特别强调确定下列因素 光感受器细胞中全反式视黄醛的控制水平 确定维甲酸结合蛋白在细胞周期活动中的作用 获得有关循环中的一种酶的结构信息。 视黄酸及其载体蛋白CRABP存在于视网膜中 相对较大的数额。由于这种维甲酸不能被还原为 体内的视黄醛或视黄醇，因此不能参与视觉 循环，它很可能参与其他方面的维生素A的功能。 视网膜中维甲酸功能的问题将被解决， 专注于提供酶的分子描述和 控制参与了它的合成。 对临床视网膜疾病潜在病因的认识 需要了解产生 视觉反应。目前，详细信息的相对匮乏 关于视觉循环酶及其调控和维甲酸功能 和视网膜的生物合成，甚至排除了询问有关 可能与视网膜疾病有关。概念、结构 在此期间将获得的信息、抗体和cdna探针 项目期内将允许未来探索 视黄醇代谢对视网膜疾病的影响。