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:
This progress report includes the work of one subordinate project at the HNRCA funded through a Specific Cooperative Agreement with TUFTS UNIVERSITY. For further information and progress reports, see 1950-51000-075-02S (Using nutrition and proteolysis to delay age related macular degeneration and cataracts).
1. LAB: Nutrition and vision research: Dietary intake is related to risk for age related macular degeneration. Age related macular degeneration (AMD) is the leading cause of blindness in America and there are no known means to delay the onset and progress of this disease. ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, obtained epidemiologic information that indicates that consuming diets that release glucose into the bloodstream more slowly, called lower glycemic index diets, have lower risk for the onset and progress of AMD. We predict that with slight dietary modification to lower the dietary GI, over 100,000 people can be spared from AMD. In order to maximize the health advantages of the diet, animal models were required, but none existed. We developed the first animal model that shows AMD-like lesions are affected by the glycemic index of the diets the animals consumed. Importantly, animals that consumed the lower glycemic index diet developed lesions at far slower rates. This corroborates the human epidemiologic findings and gives us a biologic platform with which to improve the diets and determine mechanisms of action.
2. LAB: Nutrition and vision research: Elucidating mechanisms that relate dietary glycemia to retinal health. Mechanistic information regarding how dietary GI is related to risk for age related diseases such as AMD, diabetes and cardiovascular disease is critically needed in order to optimize diets and develop diet- or nutraceutical (nutrient derived pharmaceuticals)- based treatments for these diseases. We found that upon aging, proteins in animals that consumed the higher glycemic index diets were more modified by sugars (called glycation) than proteins from lower glycemic index-fed animals. These toxic “glycated” proteins accumulated in all tissues examined. These proteins are thought to be deleterious for the cells and result in limited tissue function, which might explain why several seemingly unrelated diseases show similar relations to dietary glycemic index. The results of cell culture models developed by us showed that after glycation the damaged proteins are not properly recognized by the cellular machinery that usually targets and destroys such damaged proteins. The glycation also compromises the damaged-protein recognition machinery. As a result of this research ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, have identified a vicious cycle that starts with the consumption of a higher glycemic index diet. This causes protein damage, inability to recognize the damaged material, compromised ability to degrade the damaged proteins. It results in accelerated accumulation of glycated proteins, advancing cell toxicity and compromised organfunction.
3. LAB: Nutrition and vision research: Protein degradation is related to lens formation and maintenance. Whereas AMD is the leading cause of blindness in the USA; cataract is the leading cause of blindness globally. As with AMD, there is no means to delay the onset or progress of cataract, perhaps, other than optimizing nutrition. We have spent the last two decades identifying nutrients that might prolong lens function. Because in the lens, proteins must function for a lifetime (they are the longest lived proteins in the body) it is crucial to understand when and how the proteins are formed and it is important to understand relationships between the processes that are involved in lens formation and those that are available to remove damaged proteins. During this year ARS-funded researchers at JMUSDA-HNRCA at Tufts University, Boston, MA, published the first documentation of how the protein degrading system controls lens formation. We elucidated for the first time how lens cells become the clear fiber optics that result in our ability to see, specifically how they remove their nuclei. With this information we can begin to seek new data to determine how nutrients affect these processes and to search for nutrients that can extend lens function.
Chiu, C., Liu, S., Willett, W., Wolever, T., Brand-Miller, J., Barclay, A., Taylor, A. 2011. Informing food choices and health outcomes by use of the dietary glycemic index. Nutrition Reviews. 69(4):231-242.