Molecular modulation and gene therapy in choroidal neovascularization.

1.脉络膜新生血管的分子调控通过强激光光凝后极部视网膜诱导猴眼和大鼠眼脉络膜新生血管形成。用原位杂交和免疫组织化学方法检测到新生血管中b-成纤维细胞生长因子、血管内皮生长因子、转化生长因子-β及其受体的基因表达，在新生血管形成的早期明显，晚期表达较少。这些结果提示CNV的发生和消退受这些细胞因子的调控。干扰素β对新生血管形成的影响局部或全身应用干扰素-β均可抑制新生血管的形成。新生血管的消退是由于视网膜色素上皮的增殖所致。干扰素-β上调新生血管生成因子的表达。用反义寡核苷酸或反义质粒包裹日本血凝病毒(HVJ)与脂质体联合的CNVA载体进行基因治疗的可能性，并将其导入CNV或RPE体内。这些结果表明，在CNV的治疗中，用HVJ-脂质体方法进行基因治疗将是有效的。

1. Molecular modulation in choroidal neovascularizationChoroidal neovascularization (CNV) was induced in monkey and rat eyes by intense laser photocoagulations of the retina in the posterior pole. In experimental CNV, expression of mRNA of b-fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), trans-forming growth factor (TGF)-β, and their receptors were revealed, using in situ hybridization and immunohistochemistry, markedly in the early stage in developing of CNV, and slightly in the late stage. These results suggest development and regression of CNV were modulated by these cytokines.2. Effect of Interferron β on development of CNVLocal (subtenon) or systemic administration of Interferron (IFN)-β inhibited development of CNV.Involution of CNV were due to enclosure by proliferatin of the retinal pigment epithelium (RPE). IFN-β upregulated expression of angiogenicfactors such as bFGF and VEGF in CNV.3. Possibility of gene therapy in CNVA vector of combination of hemagglutinating Virus of Japan (HVJ) and liposome was enveloped with antisense-olignucleotide or antisense plasmid, then intoroduced to CNV or RPE in vivo. They were successfully transferred in the target cells.These results show gene therapy with HVJ-liposome method will be achieved effectively in CNV treatment.