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

我们测定了激光光凝后培养的人视网膜色素上皮（RPE）细胞和大鼠视网膜中细胞因子表达的变化。我们发现色素上皮衍生因子（PEDF）上调，血管生成因子下调，即，血管内皮生长因子（VEGF）的表达，提示PEDF通过其抗血管生成活性抑制新生血管的形成，并研究了PEDF和VEGF在实验性脉络膜新生血管（CNV）大鼠模型中的表达，证实PEDF与CNV的消退有关。我们评估了LacZ基因和双链寡脱氧核苷酸（=诱饵）的日本血凝病毒（HVJ）脂质体法与玻璃体内注射在同一模型中的转染。转染NFk-B的诱骗物能有效抑制CNV的发生。因此，我们的研究结果表明，HVJ脂质体方法可以作为一种基因治疗系统，用于调节细胞凋亡， ...更多信息 缺血再灌注损伤模型是一种视网膜变性模型，表现为视网膜神经细胞凋亡。给予PEDF对视网膜细胞具有神经保护作用。本文报道了糖尿病视网膜病变、孔源性视网膜脱离和增生性玻璃体视网膜病变患者玻璃体中PEDF和VEGF的水平。糖尿病视网膜病变和增生性玻璃体视网膜病变玻璃体中PEDF含量低，而视网膜脱离玻璃体中PEDF含量高。这些结果表明，PEDF抑制血管生成和细胞增殖，并且PEDF的低浓度可能导致活动性增殖性糖尿病视网膜病变和增殖性玻璃体视网膜病变。结果还表明，在孔源性视网膜脱离的眼睛中，较高水平的PEDF可能作为视网膜脱离的神经保护剂。少

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