The most common form of inherited human blindness is retinitis pigmentosa, a family of disorders in which the photoreceptor cells of the retina progressively degenerate and disappear over a period of years. The paucity of human donor tissues at early stages of these diseases has led scientists worldwide to turn to similar retinal degeneration mutations in laboratory animals. These animal models of the human diseases have played a prominent role in vision research in the past several decades, and much has been learned from them about the cellular mechanisms of inherited photoreceptor degenerations and potential therapeutic measures for these diseases. Among the various species with retinal degenerations, mice and rats have been used most extensively, primarily because of the experimental advantages of short gestation time; small size; powerful genetic control in the form of several readily available retinal degeneration mutants, multiple inbred and congenic strains with genetic controls and different eye pigmentation types; and the potential to carry out certain embryological procedures such as the production of experimental chimeras and transgenic mice and rats. The rapidly escalating costs to maintain animal colonies on individual grant budgets are beyond the means of most vision scientists, and most investigators do not have the time or expertise in mammalian genetics to develop or maintain various inbred, congenic, coisogenic and transgenic rodent strains. Thus, the goals of this proposal are 1) to maintain breeding colonies of such mice and rats that are appropriate for studies on various forms of inherited and environmentally induced retinal degenerations, and 2) to distribute these animals and eye tissues to investigators who request them. The lines that will be developed and/or maintained and distributed are 1) Royal College of Surgeons (RCS) rats with inherited retinal dystrophy; 2) three rat strains congenic with RCS that serve as genetic controls and with different eye pigmentation and rates of retinal degeneration; 3) F344-c/+ congenic strain of rats that provides albino and pigmented littermates that are optimal for studying the role of eye pigmentation in light damage, visual system development, drug sequestration in the eye, and other aspects of ocular pigmentation; 4) transgenic rat lines with different forms of retinal degeneration; 5) congenic control mice for the retinal degeneration slow (rds) strain; and 6) albino mice that have a genetically regulated resistance to the damaging effects of excessive light. Based on past performance, this colony and the distribution of animals will benefit scores of vision scientists and will have a major impact on research leading to the causes, prevention and treatment of inherited and environmentally induced retinal degenerations.
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