Year 3

This project is to develop a new treatment for age-related macular degeneration (AMD) based on transplantation of retinal pigment epithelial (RPE) cells into the subretinal space of a patient’s eyes. These RPE cells are induced from stem cells collected from the same patient, to avoid the problem of immune rejection. AMD is primarily an inflammatory disorder caused by inappropriate attack of RPE cells by the complement system. Accordingly, negative regulators of complement activation will be expressed in the stem-cell derived RPE cells by viral transduction. We explored two sources of stem cells that can be collected from a patient: embryonic stem cells and induced pluripotent stem (iPS) cells from skin fibroblasts. We successfully programed these stem cells into fully functional RPE cells. Our team has extensive experience with the biochemistry and cell biology of the RPE. We used “knockout” mouse models with mutations in RPE genes to test the efficiency of RPE-cell transplantation. Next, we planned to test the strategy of protecting RPE cells from complement attack by over-expressing complement negative-regulatory factors. We tested the long-term viability of induced RPE cells, and rule-out tumorgenicity by transplanting these cells into the eyes of severe-combined immunodeficient mice.