Autologous Transplantation of Genetically Modified Iris Pigment Epithelial (IPE) Cells: a New Concept for the Treatment of Age Related Macular Degeneration (ARMD) and Other Disorders of the Eye

Abstract

Abstract: : Purpose: We tested the hypothesis that the subretinal transplantation of genetically modified IPE cells to express biological therapeutics might be a promising strategy for the treatment of ARMD and other retinal disorders in 3 rat models for choroidal and retinal neovascularization and photoreceptor degeneration respectively. Methods: IPE cells were transfected with high-capacity adenoviral vector coding for pigment epithelium derived factor (HC-Ad-PEDF). The transfected IPE cells were transplanted into the subretinal space. One week later the rats received 3-4 laser burns adjacent to the transplanted cells. New formation of endothelial cells was examined after 10 days. In an other set of experiments we transplanted PEDF expressing IPE cells into the subretinal space of young rats with retinal neovascularization induced by hyperoxia and 18 days old RCS rats. In flatmount preparations PEDF and newly formed endothelial cells were labeled by antibodies and measured by computer assisted morphometry. Photoreceptors were counted and labeled by rhodopsin antibodies in paraffin sections. For statistical analysis student´s t Test was performed. Results: Transplanted PEDF overexpressing IPE cells significantly inhibited pathological choroidal neovascularization in rats with laser-induced rupture of Bruch's membrane and retinal neovascularization in oxygen induced ischemic retinopathy. PEDF expressing IPE transplants also significantly increased the survival and preserved rhodopsin expression of photoreceptor cells in RCS rats during 2 month. Conclusion: These findings suggest transplantation of genetically modified IPE cells has rescue effects in 3 different animal models with eye pathologies and may be a new concept for the treatment of ARMD and other retinal disorders.

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