Transplantation of Autologous Iris Pigment Epithelium After Removal of Choroidal Neovascular Membranes

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Abstract
A NUMBER of investigators have postulated that the transplantation of retinal pigment epithelial (RPE) cells may be a useful approach for the treatment of age-related macular degeneration (AMD). However, the transplantation of fetal RPE cells in human subjects has resulted in rejection caused by slow host-graft response.1,2 To prevent rejection, it would be necessary to transplant autologous RPE cells; however, to obtain autologous RPE cells for transplantation is difficult. On the other hand, autologous iris pigment epithelial cells (IPE), which share the same embryonic origin as RPE, can be readily obtained by rather simple surgical procedures. Previous studies have demonstrated that RPE and IPE have in common a number of important properties, such as pigmentation, cellular morphology, and tight junctions.3-7 In addition, it has been shown that in vitro human, porcine, and rat IPE cells acquire the ability to phagocytize photoreceptor outer segments (ROS), which is a specific property of RPE cells in situ.8-10 It has been also shown that in rabbits autologous IPE cells can be transplanted to the subretinal space, where they form a monolayer on top of the original RPE, phagocytize ROS, develop microvilli, establish contact with the photoreceptor outer segments, and show no evidence of rejection during a 20-week follow-up.11 Recent studies have demonstrated that bovine IPE express messenger RNA for proteins involved in retinol metabolism, namely RPE65, cellular retinoic acid binding protein, and 11-cis-dehydrogenase; however, immunohistochemistry did not reveal the presence of the protein in IPE cells in situ.12 Adult RPE and IPE cells retain the ability to transdifferentiate into other cell types, such as lens epithelial cells13,14 and neural retinal cells.15-17 Since IPE cells are phenotypically plastic, have in common many properties with RPE cells, and have a common embryonic origin, it is can be assumed that IPE cells transplanted into the subretinal space would transdifferentiate into RPE cells. Therefore, IPE cells seem to be an ideal substitute for RPE cells to be transplanted to the subretinal space of patients that have RPE degenerative diseases, or of patients who suffer traumatic loss of the RPE cell layer after subretinal surgery.

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