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United States Department of Agriculture

Agricultural Research Service

Related Topics

Research Project: USING NUTRITION AND PROTEOLYSIS TO DELAY AGE RELATED MACULAR DEGENERATION AND CATARACTS

Location: Jean Mayer Human Nutrition Research Center On Aging

2010 Annual Report


1a. Objectives (from AD-416)
1. Determine how specific foods, specific components of foods of particular patterns or dietary intake are related to eye health. 2. Identify nutritional etiologic factors that are causally related to onset, prevalence and progress of age-related macular degeneration and cataract. Design diets, dietary supplements or natural reagents to delay these diseases. 3. Identify mechanisms by which retina and lens function are maintained throughout life.


1b. Approach (from AD-416)
The objectives of the Laboratory for Nutrition and Vision Research are to find nutritional means to diminish the prevalence or delay the onset or progress of age related eye diseases such as cataract and age-related macular degeneration. These are the major blinding diseases. We approach these objectives using epidemiologic and laboratory techniques. At present we are analyzing nutritional, ophthalmologic and genetic data from about 15,000 people. Studies in the laboratory are oriented to determine the pathobiologic mechanisms that underlie the epidemiologic observations. Thus, we are trying to understand how consuming a diet that provides high levels of readily digested carbohydrate (dietary glycemic index) is related to increased risk for macular degeneration and cataract. We are also trying to understand why antioxidants confer visual benefit. A complementary aspect of this work involves elucidation how the proteolytic machinery specifically, and the protein quality control machinery in general, is related to maintaining proper protein quality within lens and retina cells. Another aspect of this work involves trying to understand how this proteolytic machinery controls tissue formation and integrity and how its function is related to nutrition.


3. Progress Report
Loss of sight is among the greatest fears for the elderly, leading to compromised life quality, loss of productivity, and high costs. We continue to focus on ways to preserve visual function because means to remediate lost vision are still not available, treatments that can delay loss of vision that is already in progress are of limited value, and it is always better to preserve vision rather than try to recapture it. Our approaches involve elucidating biochemical mechanisms to support findings from epidemiologic studies that show that consuming lower glycemic index diets is related to prolonged retina and lens function, and that the effects of dietary glycemia are complementary to effects on vision of other dietary components. This mechanistic approach is critical since there will probably never be an intervention trial regarding glycemic index and risk for onset or progress of age-related eye disease due to the time that such a study might require, and the fact that it might be unethical to do so since it is already established that consuming higher glycemic index diets is associated with elevated risk for heart disease and type 2 diabetes. We also expand our epidemiologic efforts to include additional data bases from new cohorts and compare our data with data from other cohorts. Small scale animal studies to test the hypothesis that consuming lower glycemic index diets is associated with diminished risk for indicators of early age-related macular degeneration are progressing well and the large volume of novel data we obtained compels us to scale these experiments up and also to try new, additional animal models with this dietary regime. Scaling up will allow us to investigate additional biochemical phenomena and new animal models are useful because they are affected by an alteration in the gene that was recently identified as causally related to risk for macular degeneration. Thus they model as closely as possible the human condition. It is well established that many age related syndromes are associated with the accumulation of damaged proteins. Because of this we are continuing to elucidate functions for the ubiquitin and lysosomal proteolytic pathways in the lens and retina. An unexpected fining is that the ubiquitin pathway also directs the proper differentiation and development in the lens. Specifically we solved an age-old enigma of how lens cells removes their cell nuclei. This is required for proper passage of light through the lens and failure to do so is associated with cataract. The data suggest that eventually, control of ubiquitin pathway genes may be used to remediate the lens or even rebuild a damaged lens. Additional work focuses again on lutein and its utility in the lens and retina. For publications relating to this project, see parent project #1950-51000-075-00D.


4. Accomplishments

Last Modified: 10/20/2017
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