The importance of macrophage senescence in regulating angiogenesis in macular degeneration
How does cholesterol within drusen influence macrophage function in age-related macular degeneration? Does it promote the conversion of macrophages to pro-angiogenic cells that, in turn, cause progression to neovascular disease?
Our proposal will address whether cholesterol in drusen seen during the early stages of macular degeneration causes dysfunctional activation of macrophages and advancement to neovascular age-related macular degeneration (AMD). We will use morphologic (structural), functional, and genetic approaches to test this hypothesis.
Public Health Relevance: Age-related macular degeneration is the leading cause of blindness in people over 50 years of age. Mechanisms that lead to immune dysfunction as identified in this proposal that are relevant to the pathophysiology of abnormal angiogenesis will help us devise immune based therapies that ameliorate disease progression and ultimately blindness.
Although epidemiologic studies suggest that statins that lower cholesterol reduce the risk of progression in AMD, our study is unique in that it directly evaluates the role of cholesterol within drusen during the progression of AMD.