The Role of A2E in RPE Atrophy

Janet Sparrow, PhD
Trustees of Columbia University (New York, NY)
Year Awarded:
2002
Grant Duration:
April 1, 2002 to March 31, 2003
Disease:
Macular Degeneration
Award Amount:
$50,000
Grant Reference ID:
M2002043
Award Type:
Standard
Award Region:
US Northeastern

The Role of A2E in RPE Atrophy

Details

The death of retinal pigment epithelial (RPE) cells in age-related macular degeneration (AMD) precedes the degeneration of photoreceptor cells and the loss of vision. One factor that places RPE cells at risk is the accumulation of lipofucsin fluorophores. A major fluorophore of RPE lipofuscin is A2E, which may be responsible for light-mediated RPE cell death. Dr. Sparrow has hypothesized that with light exposure, A2E within the cells undergoes chemical changes that produce reactive intermediates, which cause cell injury. Furthermore, she has proposed that the target of these reactive intermediates is cellular DNA. To test her hypotheses, Dr. Sparrow is using an RPE cell culture model in which the intracellular levels of A2E can be manipulated and the DNA can be analyzed. The goal of this work is to develop therapies that would reduce the formation of A2E, destroy this molecule within the RPE cell, or prevent the events initiated by A2E that cause cell damage. The accumulation of A2E in RPE is particularly relevant to atrophic (dry) AMD, and if successful, this study could provide a basis for the development of a treatment for the dry form of the disease.
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