Genetic Variability in the Vitamin A Cycle in AMD

Project Summary

Despite numerous studies, few environmental factors have been identified as possible causes of AMD. However, there is evidence suggesting that some people have a genetic predisposition for AMD, even though the possible gene mutations have yet to be identified. Dr. Thompson hopes to discover the possible genetic alterations that contribute to AMD. Her hypothesis is based upon the belief that many age-related diseases may be due to multiple minor defects in genes involved in a common physiological or biochemical process. She is also acting on an observation that mutations in genes involved in vitamin A metabolism are responsible for early-onset retinal diseases. She has proposed that multiple minor genetic defects affecting the conversion of vitamin A into 11-cis retinal, or the cycling of metabolic intermediates between RPE and photoreceptors, may be responsible for AMD. To test this hypothesis Dr. Thompson seeks to: 1) identify polymorphisms (genetic differences in a population that may or may not have any functional consequences) in genes involved in vitamin A metabolism; 2) determine the frequencies of these genetic changes in AMD patients versus the general population; and 3) determine whether there is an association of certain genetic changes, or combinations of changes, and the susceptibility to AMD. Identifying AMD susceptibility genes is a critical goal in the field that could lead to effective treatments in the future.