Subretinal transplantation of retinal pigment epithelium overexpressing fibulin-5 inhibits laser-induced choroidal neovascularization in rats.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Choroidal neovascularization (CNV) is the abnormal angiogenesis that causes severe visual loss in AMD. Fibulin-5 (Fbln5), which functions as an angiogenesis inhibitor, plays an important role in the pathogenesis of AMD. Here, we investigated whether subretinal transplantation of Fbln5-overexpressing retinal pigment epithelial (RPE) cells can inhibit CNV in vivo. Adult Long-Evans rats were used in this study. CNV was induced by laser photocoagulation. One week after laser-induced CNV, RPE cells expressing pZlen-Fbln5-IRES-GFP or the control pZlen-IRES-GFP vectors were transplanted into the subretinal space of the right and left eyes, respectively. CNV was evaluated using fundus photography, fundus fluorescein angiography (FFA), and hematoxylin and eosin staining. We found that CNV occurred at 1 week after photocoagulation, reaching peak activity at 3 weeks and remaining at a high level at 4-5 weeks after photocoagulation. Transplanted RPE cells survived for at least 4 weeks and migrated toward the retina. Subretinal transplantation of Fbln5-overexpressing RPE cells resulted in a significant reduction in the total area of leakage and the number of leakage spots compared with transplantation of RPE cells expressing only green fluorescent protein. Our findings suggest that subretinal transplantation of Fbln5-overexpressing RPE cells inhibits laser-induced CNV in rats and thus represents a promising therapy for the treatment of AMD.