Retinal Neovascularization Is Prevented By Blockade Of The Renin-Angiotensin System

ObjectiveTo investigate a possible role for the renin-angiotensin system (RAS) in the development of retinal neovascularization and the effect of angiotensin converting enzyme inhibitor (ACEI) and angiotensin type 1 receptor blocker (ARB) on suppressing retinal neovascularization.MethodsIt was a random control experimental study. Eighty seven-day-old C57BL/6J mice were divided into four groups randomly including normal control group, hyperoxia model group, ACEI group and ARB group, twenty in each group. ACEI group, ARB group and hyperoxia model group were exposed to 75% oxygen to establish a model of oxygen-induced retinopathy, and received daily intraperitoneal injections of captopril 10 mg/kg, valsartan 40 mg/kg and the equal amount of saline respectively for five days continuously after leaving oxygen box. Fluorescent angiography was used to assess the vascular pattern of retina. The proliferative neovascular response was quantified by counting the nuclei of new vessels extending from the retina into the vitreous in cross-sections. AngiotensinⅡ(AngⅡ) and vascular endothelial growth factor (VEGF) protein levels in retinas were measured by Western blot. Significant differences between groups were evaluated by one-way analysis of variance, followed by Dunnett-t test and Pearson correlation analysis. Statictical difference was considered significant at a P value less than 0.05.ResultsFluorescent angiography presented increasing neovascular tufts with fluorescein leakage in hyperoxia model group compared to the normal control group. Neovascular tufts and fluorescein leakage were decreased in ACEI group and ARB group especially in ACEI group compared to the hyperoxia model group. The number of endothelial cells of new vessels extending from retina to vitreous were increased significantly in hyperoxia model group (43.23±2.57) as compared with normal control group (1.37±0.93) (P=0.00), while decreased significantly in ACEI group (15.27±1.76) and ARB group (27.60±2.25) especially the former as compared with hyperoxia model group (F =2439.00, P=0.00). The expression of AngⅡprotein in retinas were increased significantly in hyperoxia model group (0.365±0.004) as compared with normal control group (0.035±0.003) (P=0.00), while decreased significantly in ACEI group (0.078±0.004)and ARB group (0.163±0.005) especially the former as compared with hyperoxia model group (F=4249.00, P=0.00). The expression of VEGF protein in retinas were increased significantly in hyperoxia model group (0.372±0.004) as compared with normal control group (0.049±0.007) (P=0.00), while decreased significantly in ACEI group (0.084±0.005) and ARB group (0.197±0.004) especially the former as compared with hyperoxia model group (F=2443.00, P=0.00).ConclusionsRAS participated in the occurrence and development of retinal neovascularization via the upregulation the expression of VEGF. Early treatment with ACEI and ARB could improve retinal neovascularization to some degree and protect the retinas. The effect of treatment with ACEI was better than that with ARB in short term situation.