Subretinal transplantation of genetically modified human cell lines attenuates loss of visual function in dystrophic rats

Royal College of Surgeons rats are genetically predisposed to undergo signi ficant visual loss caused by a primary dysfunction of retinal pigment epith elial (RPE) cells. By using this model, we have examined the efficacy of su bretinal transplantation of two independent human RIPE cell lines each exhi biting genetic modifications that confer long-term stability in vitro. The two cell lines, a spontaneously derived cell line (ARPE19) and an extensive ly characterized genetically engineered human RIPE cell line (h1RPE7), whic h expresses SV40 large T (tumor) antigen, were evaluated separately. Both l ines result in a significant preservation of visual function as assessed by either behavioral or physiological techniques. This attenuation of visual loss correlates with photoreceptor survival and the presence of donor cells in the areas of rescued photoreceptors at 5 months postgrafting (6 months of age). These results demonstrate the potential of genetically modified hu man RPE cells for ultimate application in therapeutic transplantation strat egies for retinal degenerative diseases caused by RIPE dysfunction.