A2E, Lipofuscin, and Macular Pigments in a Primate Model of AMD
CollaboratorPaul S. Bernstein, MD, PhD University of Utah
Age-related macular degeneration (AMD) is the most common cause of legal blindness in the elderly in developed countries, and is a leading cause of blindness worldwide. The typical American diet is low in nutritional factors that may reduce the risk or severity of AMD. The goal of this project is to determine whether being deprived of these nutrients has consequences for the development of AMD, and to determine the mechanisms by which this occurs. Results from these studies will provide direct evidence for the importance of these nutritional factors in maintaining retinal health and preventing advanced retinal disease, and may reveal new options for therapeutic intervention.
The goal of this project is to understand the long-term effects and impact that deprivation of nutritional factors known to be important for retinal health can have on development of macular degeneration. We have two specific aims for these studies. First is to quantify and correlate measurements of retinal health (fundus autofluorescence, FAF) with measurements of macular pigment (macular pigment optical density, MPOD) in vivo throughout the lifespan in animals fed normal diets and in aged animals fed diets deprived of carotenoids that are ,composed to form macular pigment. To satisfy this aim, we are performing FAF and MPOD retinal imaging in 40 monkeys fed normal diets throughout the lifespan. We then analyze these images to quantify the levels of autofluorescence and macular pigment across the macula and correlate these measurements to determine spatial relationships between the factors. The goal is to determine whether increased MPOD affects measurements of FAF, and if so, whether it does so in a spatially important way for macular and visual health. The second aim is to correlate the biochemical components of FAF and MPOD in tissue. To do so, we are collecting eyes from monkeys fed normal diets throughout the lifespan and processing them for biochemical and histological study. We have previously collected eyes from animals fed lifelong diets devoid of macular pigment and are performing biochemical and histological analysis on these tissues. The goal of these studies is to correlate measurements of the biochemical components of diet with the in vivo measures so as to confirm the cause of the relationships determined in Aim 1.
This proposal is unique because we are using two animal resources not available anywhere else in the world: an aging monkey resource and our cohorts of animals (now over 20 years old) that have been raised on life-long diets devoid of macular pigment. We also have built one of the most comprehensive and state-of-the-art retinal imaging and retinal function assessment labs for non-human primates in the world. Finally, we have the unique ability, unlike clinical studies, to perform correlative studies between in vivo measurements and biochemical and histological measurements obtained from the same tissue.
Upon completion, our studies will determine the relationship between nutritional factors involved in retinal health and the development of macular disease. These results can be expected to inform the field regarding diet supplements shown to minimize disease progression, identify targets for future therapeutic development, and ultimately provide critical data to aid in reducing the prevalence and impact of AMD.