Interaction of Diet and Genotype in AMD Pathogenesis

Project Summary

Age-related macular degeneration is the predominant cause of vision loss in adults over 65. There is no single cause for this disease, and it results from complex interactions of genetic predisposition and environmental influences. Consequently, it is difficult to predict, and to treat. Lack of effective treatment stems from both the complexity of the disease, and lack of good animal models in which to study it. We have been able to obtain a mouse model that carries a mutation in an important macular degeneration gene - Factor H. Using this mouse as the basis of our experiments, we will superimpose additional mutations (ApoE and CCr2) and environmental conditions (high fat diet). We expect that these interventions hasten onset of AMD in mice. We will also determine whether mice carrying a mutation in Tlr4, a gene that has recently been associated with AMD, develop AMD-like lesions after normal or high fat feeding. The intent of this is to develop a robust early onset mouse model of AMD for therapeutic testing. These experiments also provide insight into how diet interacts with predisposing genetic burden to create AMD pathology. Understanding these relationships will enhance the capacity of the clinician to council at-risk patients.