Dietary Factors in Retinal Aging and Macular Disease

视网膜衰老和黄斑疾病的饮食因素

• 批准号: 9769030
• 负责人: MARTHA NEURINGER
• 金额: $ 50.07万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769030
• 关键词: Address; Age; Age related macular degeneration; Aging; American; American diet; Animal Model; Animals; Antioxidants; Atrophic; Biochemical; Blindness; Carotenoids; Cells; Clinical Research; Data; Developed Countries; Developing Countries; Development; Diet; Dietary Factors; Dietary Fats; Dietary History; Disease; Disease Progression; Elderly; Evolution; Eye; Eye diseases; Fatty acid glycerol esters; Fundus; Genetic; Goals; Health; High Fat Diet; Histologic; Human; Intake; Intervention; Joints; Knowledge; Lead; Legal Blindness; Life; Lipofuscin; Longevity; Lutein; Macaca; Macaca mulatta; Measurement; Measures; Modality; Modeling; Molecular; Monkeys; Morphology; Nature; Nutrient; Nutritional; Omega-3 Fatty Acids; Outcome; Pathology; Patients; Pigments; Play; Prevalence; Prevention; Primates; Process; Public Health; Research; Resources; Retina; Retinal; Retinal Diseases; Risk; Risk Factors; Role; Smoking; Structure; Testing; Therapeutic Intervention; Thick; Work; age related; base; comparison group; dietary supplements; disorder of macula of retina; disorder prevention; effective therapy; fovea centralis; geographic atrophy; good diet; imaging modality; in vivo; in vivo imaging; indexing; macula; new therapeutic target; nonhuman primate; normal aging; nutrition; premature; prevent; retinal imaging; standard of care; sugar; translational model; zeaxanthin

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.

项目概要 年龄相关性黄斑变性（AMD）是老年人法定失明的最常见原因 发达国家和全世界失明的主要原因。越来越多的证据支持这一点。 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)， 典型的 omega-3 (ω-3) 脂肪酸集中在黄斑部形成黄斑色素。 美国饮食中这些营养素含量较低，因此迫切需要更好地了解这些营养素的作用 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。 具有黄斑和中央凹的灵长类动物提供了一个准确的翻译模型来解决这个问题。 可用三种特殊资源： 终生控制饮食、缺乏营养的老年猕猴群体 L 和 Z 并提供足够或不足的 ω-3 脂肪酸含量，并显示出早期 AMD 的迹象； 老年猴子的饮食富含脂肪和糖，并模仿典型的美国饮食和一大群猴子； 喂养健康饮食的衰老猕猴以解决正常衰老的影响。 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和 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 眼睛跨越整个生命周期和广泛的饮食史，包括终生 缺少 L/Z。 2) 定义L/Z、脂褐素分子成分、视网膜之间的离体关系 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 体内获得的测量值。 总的来说，这些目标将量化黄斑色素的纵向变化以及浓度和 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，并将体内和离体评估之间的这些测量值相关联 增强体内成像解释的方式。 我们期望拟议工作的结果将对角色的理解产生重大影响 我们还希望提供黄斑色素和膳食脂肪在衰老和视网膜疾病（包括 AMD）中的作用。 我们的研究也将为当前关于脂褐质成分在 AMD 中的作用的争论提供关键信息。 检查视网膜老化和疾病的演变以及获得高质量的绝佳机会 由于视网膜健康的高度转化性质，临床病理学相关性。 在这些非人类灵长类动物研究中，预计它们将对理解 营养在维持视网膜健康和预防或治疗视网膜疾病方面的作用。