Location: Jean Mayer Human Nutrition Research Center On Aging
Project Number: 8050-51000-089-001-S
Project Type: Non-Assistance Cooperative Agreement
Start Date: May 1, 2014
End Date: Apr 30, 2019
Objective:
LAB NAME: Nutrition and Vision Research
1. Determine how the interactions of specific foods/food components/dietary patterns with individual or population genetics are related to eye health during aging, and to aging per se.
1.1a - Laboratory animal experiments to determine nutrient-gene interactions
1.1b – Exploiting lower dietary GI to delay AMD
1.2 - Determine how intake of groups of foods affect risk for AMD and cataract and how these relationships are altered by genetics.
2. Identify nutritional etiologic factors that are causally related to onset, prevalence and progress of age-related macular degeneration and cataract. Identify mechanisms by which retina and lens functions are maintained throughout life.
2.1 –To determine if lutein/zeaxanthin and DHA supplementation can delay AMD-like features in UPS-compromised mice.
2.2- To investigate the ability of CHIP over-expression to enhance cellular capacity to degrade and/or refold damaged proteins we will use cataract-causing mutant proteins (R49C aA -, R120G aB - and T5P 'C-crystallins) as substrates in cultured lens epithelial cells or lens fibers in vivo.
2.3-UbcH7 works with a subset of its cognate ubiquitin ligase partners to affect cell migration.
3. Find new biomarkers of tissue function using readily available samples, i.e., blood, tears, cornea, skin, for in vivo assessment.
4. Determine how diet is related to the microbiome and eye health during aging.
Approach:
LAB NAME: Nutrition and Vision Research
Use of clinical epidemiologic studies to survey large human cohorts. Laboratory systems are exploited to model the diseases and elucidate mechanisms of action of potentially salutary modalities. At present, we are analyzing nutritional, ophthalmologic and genetic data from about 20,000 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 (high dietary glycemic index) is related to increased risk for macular degeneration and cataract. The studies are complemented by investigations into the metabolome and microbiome, in order to gain a wholistic understanding of mechanisms by which nutrition affects function. We are also trying to understand why and how antioxidants confer visual benefit. A complementary aspect of this work involves elucidation how the cellular protein quality control machinery (lysosomal and cytoplasmic proteolytic capacities) are 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 and varies over time or stress.
