): The ultimate aim of this research is to find genes that influence the severity and/or course of human retinal degenerative diseases; specifically, to find the alleles of such genes that reduce the severity and/or prolong the advance of symptoms. The approach is to first find retinal-degeneration modifying genes in animal models. The work involves two models: albino mice that show differences in age-related retinal degeneration relative to strain type, and albino mice inheriting pcd (Purkinje cell degeneration) disease. The albino pcd mice also show strain differences in retinal degeneration after light overexposure. The approach is to analyze the progeny of two types of genetic crosses: the first between two mouse strains that differ significantly in the degree of retinal degeneration they undergo as they age, and the second, between pcd strains that differ significantly in the exacerbation of retinal degeneration they undergo after exposure to excess light. Since the factors that influence retinal degeneration are complex, quantitative genetics analyses will be used to discover the chromosomal loci of the modifier genes that influence these retinal degenerations. Once the loci are found, the individual genes that are active in these loci will be identified with the use of genetic maps and other databases, and evaluated with the tools of molecular biology. The protective gene alleles themselves, or their mechanisms of action, will open avenues of study leading to gene or pharmaceutical therapies for human retinal degenerations. Since there are so many different primary causes of human retinal degenerative disease, it would be of great benefit if any one of the modifying genes found in this study protects against retinal degenerations that have several different causes; this would make therapeutic approaches simpler.
