Department of Biological Sciences, Allergan, Inc., Irvine, California 92612-1599, USA.
Invest Ophthalmol Vis Sci. 2011 Jul 20;52(8):5424-31. doi: 10.1167/iovs.10-6262.
To determine whether chronic treatment with brimonidine (BRI) attenuates retinal vascular leakage and neovascularization in neonatal mice after exposure to high oxygen in a mouse model of retinopathy of prematurity (ROP), and choroidal neovascularization (CNV) in rats after laser treatment.
Experimental CNV was induced by laser treatment in Brown Norway (BN) rats. BRI or vehicle (VEH) was administered by osmotic minipumps, and CNV formation was measured 11 days after laser treatment. Oxygen-induced retinopathy was generated in neonatal mice by exposure to 75% oxygen from postnatal day (P)7 to P12. BRI or VEH was administered by gavage, and vitreoretinal vascular endothelial growth factor (VEGF) concentrations and retinal vascular leakage, neovascularization, and vaso-obliteration were measured on P17. Experimental CNV was induced in rabbits by subretinal lipopolysaccharide/fibroblast growth factor-2 injection.
Systemic BRI treatment significantly attenuated laser-induced CNV formation in BN rats when initiated 3 days before or within 1 hour after laser treatment. BRI treatment initiated during exposure to high oxygen significantly attenuated vitreoretinal VEGF concentrations, retinal vascular leakage, and retinal neovascularization in P17 mice subjected to oxygen-induced retinopathy. Intravitreal treatment with BRI had no effect on CNV formation in a rabbit model of nonischemic angiogenesis.
BRI treatment significantly attenuated vitreoretinal VEGF concentrations, retinal vascular leakage, and retinal and choroidal neovascularization in animal models of ROP and CNV. BRI may inhibit underlying event(s) of ischemia responsible for upregulation of vitreoretinal VEGF and thus reduce vascular leakage and retinal-choroidal neovascularization.
在早产儿视网膜病变（ROP）的小鼠模型中，观察慢性溴莫尼定（BRI）治疗是否能减轻高氧暴露后新生鼠的视网膜血管渗漏和新生血管形成，以及激光治疗后大鼠脉络膜新生血管（CNV）的形成；方法：采用激光诱导 Brown Norway （BN）大鼠产生实验性 CNV，通过渗透微型泵给予 BRI 或载体（VEH）治疗，激光治疗 11 天后测量 CNV 形成情况；通过将新生鼠置于 75%的氧气环境中（从出生后第 7 天到第 12 天）产生氧诱导的视网膜病变，通过灌胃给予 BRI 或 VEH 治疗，在第 17 天测量玻璃体内视网膜血管内皮生长因子（VEGF）浓度、视网膜血管渗漏、新生血管形成和血管闭塞情况；通过向兔眼视网膜下注射脂多糖/成纤维细胞生长因子-2 诱导实验性 CNV；结果：当在激光治疗前 3 天或激光治疗后 1 小时内开始全身性 BRI 治疗时，可显著减轻 BN 大鼠激光诱导的 CNV 形成；当在高氧暴露期间开始 BRI 治疗时，可显著降低氧诱导的 ROP 新生鼠玻璃体 VEGF 浓度、视网膜血管渗漏和视网膜新生血管形成；兔眼非缺血性血管生成模型中玻璃体内 BRI 治疗对 CNV 形成无影响；结论：BRI 治疗可显著降低 ROP 和 CNV 动物模型中玻璃体内 VEGF 浓度、视网膜血管渗漏和视网膜及脉络膜新生血管形成，BRI 可能抑制了导致玻璃体内 VEGF 上调的缺血相关事件，从而减少了血管渗漏和视网膜-脉络膜新生血管形成。
