Gene Therapy and Transplantation of Retinal Pigment Epithelium for Ocular Proliferative Deseases and Retinal Degeneration

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1. We investigated mRNA expression of vascular endothelial growth factor (VEGF) and its receptor, KDR in a rat model of experimental choroidal neovascularization (CNV) and demonstrated that VEGF attibutes the development of CNV in an autocrine and/or a paracrine mammer.We evaluated the transfection of oligodeoxynucleotides (ODNs), double stranded oligodeoxynucleotides(=decoy) and LacZ gene by means of the hemagglutinating virus of Japan (HVJ) liposome method with intravirreoul injection in a same model.We conclude that the HVJ liposome method achieved effective gene transfer into CNV tissue, and thus, this method can be used as agene therapy system for regulation of angiogenic factors to treat the CNV in vivo.Ornitine induced retinopathy and ischemia-reperfusion injury model those are retinal degeneration model showed apoptosis in retinal neuronal cells. Expression of neuroprotective factors, basis fibroblast growth factor (bFGF) and Midkine was up-regulated in tischemia-reperfusion injury model and up-regulation of VEGF was observed only transiently.Human bFGF sense cDNA or antisense cDNA can be efficiently introduced into cultured RPE cells by electroporation methods. The successful expression of the genes into RPE cells demonstrated that this technique can be used to regulate cytokine expression which protects neurons or inhibits angiogenesis and thus increase the scope of RPE transplantation for the treatment of CNV or retinal degeneration.