Dietary Factors in Retinal Aging and Macular Disease

项目摘要 视网膜相关性黄斑变性（AMD）是老年人法律的失明的最常见原因， 发达国家和全球失明的主要原因。越来越多的证据表明 营养因子的保护作用，包括类胡萝卜素叶黄素（L）和玉米黄质（Z）， 集中在中央凹形成黄斑色素和ω-3脂肪酸。然而，典型的 美国人的饮食中这些营养素含量很低，因此，迫切需要更好地了解 这些营养素在视网膜老化和疾病中发挥作用，并具有降低AMD风险的潜力。只有非人类 具有黄斑和中央凹的灵长类动物提供了解决该问题的精确平移模型。我们有 可用的三个特殊的资源：群体的老龄猕猴与终身控制饮食缺乏 L和Z的水平，并提供足够或不足的ω-3脂肪酸含量，并显示早期AMD的迹象; 年老的猴子吃高脂肪和高糖的食物，模仿典型的美国饮食; 老年猕猴喂养健康的饮食，以解决正常老化的影响。这些群体的比较 动物提供了一个真正独特的机会来了解饮食因素在视网膜衰老中的作用， 疾病该提案将利用这些独特的资源来实现以下目标： 1)定义灵长类动物黄斑色素与黄斑健康指标之间的体内关系 眼睛在整个生命周期和广泛的饮食史，包括终身 没有L/Z。 2)定义离体L/Z、脂岩藻素的分子组分、视网膜色素变性和视网膜色素变性之间的关系。 形态学和饮食相关的视网膜病理学，并将这些发现与相应的 在体内获得的测量。 总的来说，这些目标将量化黄斑色素的纵向变化和浓度， 视网膜和RPE中脂褐素组分的分布将表征视网膜结构的变化， 年龄和视网膜疾病，并将在体内和离体评估之间关联这些测量 增强体内成像解释的模式。 我们期望拟议工作的结果将对理解这一作用产生重大影响 黄斑色素和膳食脂肪在衰老和视网膜疾病，包括AMD。我们还希望提供数据 这对目前关于脂褐质组分在AMD中的作用的争论至关重要。我们的研究还将提供 研究视网膜老化和疾病的演变，以及获得高质量的 视网膜健康的多个度量中的临床病理学相关性。由于高度的翻译性质， 在这些非人类灵长类动物的研究中，它们预计将对理解 营养在维持视网膜健康和预防或治疗视网膜疾病中的作用。

PROJECT SUMMARY Age-related macular degeneration (AMD) is the most common cause of legal blindness in the elderly in developed countries and a leading cause of blindness worldwide. A growing body of evidence supports protective roles for nutritional factors, including the carotenoids lutein (L) and zeaxanthin (Z), which concentrate in the fovea to form the macular pigment, and omega-3 (ω-3) fatty acids. However, the typical American diet is low in these nutrients and therefore, there is an urgent need to better understand the role that these nutrients play in retinal aging and disease and their potential to reduce the risk of AMD. Only nonhuman primates with a macula and fovea provide an accurate translational model to address this issue. We have available three exceptional resources: groups of aging macaque monkeys with life-long controlled diets devoid of L and Z and providing either adequate or deficient ω-3 fatty acid content, and showing signs of early AMD; aging monkeys fed diets high in fat and sugar and mimicking the typical American diet; and a large colony of aging macaques fed a healthy diet to address the effects of normal aging. Comparison of these groups of animals provide a truly unique opportunity to understand the roles of dietary factors in retinal aging and disease. This proposal will use these unique resources to address the following aims: 1) Define the relationships in vivo among macular pigment and metrics of macular health in primate eyes across the lifespan and across a wide range of dietary histories including including life-long absence of L/Z. 2) Define the relationships ex vivo among L/Z, the molecular components of lipofucsin, retinal morphology and diet-related retinal pathology, and correlate these findings to the corresponding measurements obtained in vivo. Collectively, these aims will quantify longitudinal changes in macular pigment and the concentration and distribution of components of lipofuscin in the retina and RPE, will characterize changes in retinal structure with age and retinal disease, and will correlate these measurements between in vivo and ex vivo assessment modalities to enhance the interpretation of in vivo imaging. We expect the outcome of the proposed work to have a significant impact on the understanding of the role of macular pigment and dietary fat in aging and retinal diseases including AMD. We also expect to provide data critical to the current controversy on the role of lipofuscin components in AMD. Our studies also will provide exceptional opportunities to examine the evolution of retinal aging and disease, as well as to obtain high quality clinicopathological correlations in multiple metrics of retinal health. Because of the highly translational nature of these nonhuman primate studies, they are expected to have a significantly high impact on understanding the role of nutrition in maintaining retinal health and prevention or treatment of retinal disease.