The Effect And Mechanism Of Genistein On Retinal Neovascularization And Visual Function

Retinal neovascularization occurring as a complication of diabetic retinopathy, central retinal vein occlusion and age-related macular degeneration can cause severe vision loss and blindness. Though the pathogenesis of neovascularization is still unclear, it probably results from retinal ischemia. Recent studies have implicated that vascular endothelial growth factor(VEGF) overexpression is sufficient to cause intraretinal and subretinal neovascularization.Genistein, a soy derived isoflavone, has recently attracted much attention of the medical science community. This compound was found to be a potent agent in both prophylaxis and treatment of cancer as well as other chronic diseases. The effects of genistein include inhibition of angiogenesis, tyrosine kinase phosphorylation, DNA synthesis and cell cycle arrest. But the inhibitory effects of genistein on retinal neovascularization and improvement on visual function were unknown.Retinal vein occlusion of rabbit model was established with argon laser photocoagulation to retinal vein. After one week , intravitreal injections of either 0.1 ml of 150-microM concentration of genistein, dimethyl sulfoxide (DMSO; negative control and positive control) were given every day, four days in succession .14 days after laser, the proliferated neovascular response was quantitated by counting the nuclei of endothelial cells of new vessels extending from the retina into the vitreous in 6 μm sagittal cross sections. VEGF were determined on thecross-sections after immunohistochemical stain. Before laser and 7,14 days after laser, flash electroretinogram(FERG) was recorded and statistically analyzed. Before laser and 0, 1, 7 and 14 days after laser, fluorescence fundus angiography(FFA) was performed to evaluate the retinal neovascularization .Results: 1. Rabbit with retinal vein occlusion developed severe retinal hypoxia, dramatic up-regulation of retinal neovascularization. VEGF expression was detected in inner ischemic retina and retinal neovasular tissue; The wave of FERG-b in rabbit with retinal vein occlusion was significantly scaled down( P < 0.01)that demonstrated that the changes of visual function mainly lie in the central retinal artery supplying area, i.e. from the inner nuclear layer to nerve fiber layer, there was a negative correlation between VEGF expression and the wave of FERG-b. 2. The findings include a mean of 18.19 ± 20.51 neovascular nuclei per cross-section in the non-genistein-treated retina, 12.18 ± 14.11 nuclei in genistein-treated retinal, and 0.34 ± 0.42 nuclei in the control group. VEGF stain were found stronger in the inner retinal layer of rabbit with retinal vein occlusion than in that of controls, and these were found weaker in the inner retinal layer of genistein-treated rabbit than in that of non-genistein-treated rabbit. Genistein inhibited ischemia induced retinal neovascularization. 3, The electrophysiological changes of RVO demonstrated that genistein can ameliorate visual functions. There existed statistically significant difference in latencies of FERG-a and FERG-b between pre-medicine period and post-medicine period.These results indicated that an experimental model of retinal vein occlusion was successfully produced in rabbit by argon laser photocoagulation and genistein could be an effective agent in the...