The Role of Lipofuscin Pigments and Chronic Inflammation as a Cause of Macular Degeneration

Roxana Radu, MD
UCLA - Jules Stein Eye Institute (Los Angeles, CA)
Year Awarded:
2008
Grant Duration:
April 1, 2008 to June 28, 2010
Disease:
Macular Degeneration
Award Amount:
$100,000
Grant Reference ID:
M2008090
Award Type:
Standard
Award Region:
US Southwestern
Roxana Radu, MD

Analysis of A2E-degradation and Complement Activation in Two New Animals Models for Age-related Macular Degeneration

Summary

This project will test the hypothesis that abnormal metabolism of vitamin A and its derivatives could lead to overt activation of the immune complement system. It will test this hypothesis using a well established animal model of macular defects. They will investigate the biochemical and molecular mechanisms used by the retina to deal with abnormal build-up of vitamin A-based toxic compounds.

Details

A pathologic feature of AMD is accumulation of toxic lipofuscin pigments, derived from vitamin A, in cells of the retinal pigment epithelium (RPE). This layer of cells is critical to the normal function and survival of rods and cones. Lipofuscin is a natural byproduct of photoreceptor turnover, and slowly accumulates in everyone's RPE. However, patients with AMD may have biochemical defects leading to accelerated accumulation or delayed clearance of lipofuscin pigments. When these pigments rise, the RPE loses its ability to support the photoreceptors. In time, this leads to photoreceptor death and subsequent blindness. Recent research showed that the gene for complement factor H (CFH), a component of the innate immune system, is a strong susceptibility locus for AMD. However, it is not known how dysfunction of CFH causes AMD. The study will test whether abnormal metabolism of vitamin A and its derivatives could lead to overt activation of the complement system. Studying mouse models will help us to understand the relationship between lipofuscin accumulation, complement activation, and retinal degeneration in AMD.
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