Effect of cholesterol on the aged immune system in macular degeneration

Rajendra Apte, MD, PhD
Washington University, School of Medicine (Saint Louis, MO)
Year Awarded:
2010
Grant Duration:
April 1, 2010 to March 31, 2012
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2010034
Award Type:
Standard
Award Region:
US Midwestern

The importance of macrophage senescence in regulating angiogenesis in macular degeneration

Summary

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?

Details

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.
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