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 (?-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 ?-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.
The proposed project is relevant to public health because the typical American diet is high in fat and low in carotenoids and omega-3 fatty acids, and these nutritional factors modulate the risk of age-related macular degeneration (AMD), the most common cause of legal blindness in the elderly in developed countries and a leading cause of blindness worldwide. The objective of this project is to determine the effects of these dietary factors on retinal aging and the development of age-related retinal disease, and to examine mechanisms of these effects. The results of these studies will provide direct evidence for the importance of these nutritional factors in maintaining retinal health and preventing advanced retinal disease, and will reveal new targets for therapeutic intervention.