Dietary Factors in Retinal Aging and Macular Disease

项目总结 老年性黄斑变性(AMD)是老年人法定失明的最常见原因 这是发达国家和世界范围内导致失明的主要原因。越来越多的证据支持 对营养因素的保护作用，包括类胡萝卜素叶黄素(L)和玉米黄质(Z)，它们 集中在中心凹形成黄斑色素，以及欧米茄-3(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，并有可能降低患AMD的风险。只有非人类 有黄斑和中心凹的灵长类动物提供了一个准确的转换模型来解决这个问题。我们有 可用的三种特殊资源：一群终生受控饮食的老年猕猴 L和Z型，ω-3脂肪酸含量适中或不足，有早期AMD征象； 年迈的猴子喂食高脂肪和高糖的食物，并模仿典型的美国饮食；以及一大群 老化的猕猴喂食健康的饮食，以解决正常衰老的影响。这几组人的比较 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老化和 疾病。该提案将利用这些独特的资源来实现以下目标： 1)确定灵长类动物黄斑色素与黄斑健康指标之间的活体关系 着眼于一生和广泛的饮食历史，包括终身饮食 L/Z缺席。 2)明确L/Z、脂褐素分子组成、视网膜 形态和饮食相关的视网膜病理，并将这些发现与相应的 活体测量。 总而言之，这些目标将量化黄斑色素的纵向变化和浓度和 脂褐素成分在视网膜和RPE中的分布，将表征视网膜结构的变化 年龄和视网膜疾病，并将在体内和体外评估这些测量之间的相关性 增强活体成像解释的方式。 我们预计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包括AMD在内的视网膜疾病中的作用。我们还希望提供数据 对于目前关于脂褐素成分在AMD中的作用的争议至关重要。我们的研究还将提供 检查视网膜老化和疾病演变的特殊机会，以及获得高质量 视网膜健康的多个指标之间的临床病理相关性。因为高度的翻译性 在这些非人类灵长类动物的研究中，他们预计将对理解 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.