BIOCHEMISTRY AND PHARMACOLOGY OF THE MACULAR CAROTENOIDS

人类的黄斑，负责视网膜的专门区域 对于高分辨率视力，选择性地累积两个 叶黄素-11类胡萝卜素来源于饮食、叶黄素和 玉米黄质。最近的几项流行病学研究表明 显示出饮食摄入量与 叶黄素和玉米黄质与年龄相关的进展风险 黄斑变性(AMD)是致盲的主要原因 美国的老年人。据认为，黄斑部 类胡萝卜素通过以下方式保护视网膜免受最小程度的损伤 过滤掉破坏性波长的光，并作为 抗氧化剂。 调节选择性摄取的生化机制， 黄斑类胡萝卜素的浓度和稳定性是 未知。在龙虾和蓝藻等低等动物中， 专门的类胡萝卜素结合蛋白执行这些任务。它是 假设类似的类胡萝卜素结合蛋白可能有 在人类的黄斑中也有类似的作用。这个项目的一个主要目标是 了解负责特定生物过程的生化过程 叶黄素和玉米黄素沉积在黄斑上，具有特殊的 重点是寻找潜在的类胡萝卜素结合蛋白。 该项目还将研究类胡萝卜素的性质- 蛋白质和类胡萝卜素-脂质通过定量结合相互作用 研究和各种光谱方法，包括共振 拉曼光谱，在模型系统和完整的视网膜组织中。 这一提议的实验可能会为我们提供新的见解 叶黄素和玉米黄质在体内特异性摄取的生化基础 黄斑。摄取和摄取机制的紊乱 黄斑类胡萝卜素的稳定可能会产生深远的影响 关于AMD和遗传性视网膜营养不良的进展。 预期的干预性临床研究可能能够 特定摄取系统的优势，以提高 黄斑类胡萝卜素可能会延缓或防止 由这些疾病引起的渐进性失明。

The human macula, the specialized region of the retina responsible for high resolution visual acuity, selectively accumulates two xanthophy11 carotenoids derived from the diet, lutein and zeaxanthin. Several recent epidemiological studies have demonstrated a strong inverse correlation between dietary intake of lutein and zeaxanthin and the risk of progression Age-Related Macular Degeneration (AMD) the leading cause of blindness among the elderly in the United States. It is thought that the macular carotenoids protect against least-induced damage to the retina by filtering out damaging wavelengths of light and by acting as antioxidants. The biochemical mechanisms that mediate the selective uptake, concentration, and stabilization of the macular carotenoids are unknown. In lower animals, such as lobsters and cyanobacteria, specialized carotenoid-binding proteins perform these tasks. It is hypothesized that comparable carotenoid-binding proteins may have a similar role in the human macula. A major goal of this project is to understand the biochemical processes responsible for the specific deposition of lutein and zeaxanthin the macula, with special emphasis on the search for potential carotenoid-binding proteins. This project will also investigate the properties of carotenoid- protein and carotenoid-lipid interactions through quantitative binding studies and various spectroscopic methods, including resonance Raman spectroscopy, in model systems and in intact retinal tissue. The experiments of this proposal may provide new insights into the biochemical basis of the specific uptake lutein and zeaxanthin into the macula. Derangements of the mechanisms of uptake and stabilization of the macular carotenoids could have profound impact on the progression of AMD and inherited retinal dystrophies. Anticipated interventional clinical studies may be able to take advantage of the specific uptake systems to increase the level of macular carotenoid pigment and perhaps retard or prevent the progressive blindness produced by these diseases.