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 and others, such as age-related macular degeneration, has led scientists worldwide to turn to similar retinal degenerations 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 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 and genetic procedures such as the production of experimental chimeras and transgenic animals. 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, and transgenic rodent strains. Thus, the goals of this proposal are 1) to maintain breeding colonies of such rats that are appropriate for studies on various forms of inherited and age- related 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) P23H mutant rhodopsin transgenic rat lines with 3 different rates of degeneration; and 4) S334ter mutant rhodopsin transgenic rat lines with 5 different rates of degeneration. 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 retinal degenerative diseases.
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