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
Found that consuming lower glycemic index food is associated with prolonged retinal health. Moreover, this benefit is independent of benefits gained by consuming other food items or food components such as antioxidants or omega 3 fatty acids. Using this information we are developing an algorithm that predicts who will get age related macular degeneration. Observed that the onset of many of the features of early AMD is increased by feeding C57BL6 mice high GI diets, comparable to the high GI diets that Americans consume.Importantly, we were able to delay the onset and progress of these features of early AMD by feeding the animals lower GI diets. These data confirm that consuming lower GI diets affords advantage with respect to eye health and the animal model provides a platform for testing new nutraceuticals for preservation of eye health. Completed studies which reveal mechanisms by which cells protect themselves against the stresses that are induced by exposure to sugars. Determined how perturbation of the ubiquitin proteolytic pathway alters development of the eye lens. Specific developmental processes are being identified by determining specific proteins, the expression of which is altered when the “ubiquitinome” is altered. Began to investigate how inflammation is related to eye cell function and responses to stress. Completed an analysis of the effects of dietary and bodily lutein stores on risk for specific grades of macular degeneration.