Age-related macular degeneration (AMD) is a disease that affects many in our aging population. The end result of this disease is blindness and there is no cure. Current treatments center on re-establishing contact between the neural sensory retina and its supporting tissue, the retinal pigment epithelium (RPE). There are two current surgical methods to accomplish this task, either macular translocation or RPE transplantation. Macular translocation involves detaching the retina, cutting it circumferentially, and mechanically rotating the retina such that the macula is placed onto a healthy bed of RPE. This is a very technical and difficult surgery that requires significant follow up and may not be appropriate for many patients. RPE transplantation, can in animal models of disease, rescue retinal degeneration suggesting that this may be a valuable treatment option. However, RPE grafts in AMD patients suffer a high rate of graft rejection, limiting the usefulness of this treatment. This study is focused on preparing cultures of RPE cells from adult humans that are candidates for transplantation. The proposal is based on the novel observation that coordinated cadherin adhesion causes differentiation of human RPE cells. This observation suggests that it may be possible to produce RPE monolayers in culture that function as the tissue in vivo, and may yield beneficial results for transplantation. Significantly, our data suggests that the appropriate monolayers of RPE can be produced from passaged RPE that have expanded and proliferated extensively. This new method opens the opportunity to harvest a small number of RPE from a patient, expand the cells to produce enough for transplantation, stimulate differentiation, then transplant the patient's own RPE cells back under the retina. This procedure would avoid the graft rejection problems encountered using fetal RPE cells, RPE cell lines, or cultured RPE from generic donor tissue. The goals of this pilot project are to determine whether the methods developed are broadly applicable to RPE cultures from a spectrum of donors at different ages, to determine whether the 'tissue-type' monolayers produced express the functional characteristics necessary for function after transplantation, and to determine whether the monolayers can be produced on transplantable substrates. The results from this project will significantly impact both the treatment of the disease and the basic studies that seek a cure.
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