Animal genetic models have been essential to the understanding and treatment of human retinal degenerative disease. The importance of the retinal pigment epithelium (RPE) to photoreceptor function is widely recognized. Primary degeneration of RPE cells is thought to be central to the etiology of several significant human retinal disorders including age-related macular degeneration (AMD) and pigmentary retinopathies associated with mitochondrial dysfunction, yet no animal genetic model of a primary RPE cell degeneration exists. This proposal describes a strategy to create such a model using mouse genetics. A mouse strain will be generated in which RPE cells gradually and postnatally degenerate and die due to RPE specific loss of mitochondrial function. RPE cell degeneration should induce secondary photoreceptor cell degeneration and choroidal atrophy. A detailed structural and functional analysis of the effects of RPE cell loss on the RPE and adjacent tissues will be performed at various ages. At an appropriate stage in the degeneration, the model will be perturbed by modulating light exposure. A model of primary RPE cell degeneration will be useful for understanding the interdependence of RPE and photoreceptor cells and of the RPE and choroid, for understanding pathogenic processes secondary to RPE cell death, and for investigating potential therapies in a setting in which RPE cell function is progressively compromised.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Research Grants (R03)
Project #
1R03EY014650-01
Application #
6602971
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Dudley, Peter A
Project Start
2003-04-01
Project End
2006-03-31
Budget Start
2003-04-01
Budget End
2004-03-31
Support Year
1
Fiscal Year
2003
Total Cost
$160,001
Indirect Cost
Name
Stanford University
Department
Genetics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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