Control of Ocular Proliferation and Neuroprotection by Gene Therapy and Analysis of These Molecular Mechanisms.

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We determine the changes in the expression of cytokines in cultured human retinal pigment epithelial (RPE) cells and rat retinas after laser photocoagulation. We found an up-regulation of pigment epithelium-derived factor (PEDF) and a down-regulation of angiogenic factors, i.e., vascular endothelial growth factor (VEGF) and suggested that PEDF play a role in inhibiting neovascularization by its anti-angiogenic activity.We also investigated the expression of PEDF and VEGF in a rat model of experimental choroidal neovascularization (CNV) and demonstrated that PEDF attributes the regression of CNV. We evaluated the transfection of LacZ gene and double stranded oligodeoxynucleotides(=decoy) by means of the hemagglutinating virus of Japan (HVJ) liposome method with intravitreal injection in a same model. The transfected decoy against NFk-B had effectively inhibited the development of CNV. Thus, our results suggest that the HVJ liposome method can be used as a gene therapy system for regulat … More ion of angionenic factors to treat the CNV in vivo.Ischemia-reperfusion injury model is a kind of retinal degeneration model which shows apoptosis in retina neuronal cells. Administration of PEDF had showed neuroprotective effects on retinal cells. Therefore, PEDF would be useful inpreventing neuronal degeneration in the inner retina resulting from ischemia.We reported the levels of PEDF and VEGF in the vitreous of patients with diabetic retinopathy, rhegmatogenous retinal detachment and priliferative vitreoretinopathy. PEDF in the vitreous was low in diabetic retinopathy and proliferative vitreoretinopathy, but high in rthgmatogenous retinal detachment. These results suggest that PEDF inhibits angiogenesis and cell proliferation, and that lower leverls of PEDF may result in active proliferative diabetic retinopathy and proliferative vitreoretinopathy. The results also suggest that higher levels of PEDF in the eyes with rhegmatogenous retinal detachment may act as a neuroprotective agent for the detached retina. Less