Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate
Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate
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DOI：
10.1001/archopht.1996.01100130062010
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发表时间：
1996-01-01
影响因子：
--
通讯作者：
Miller, JW
中科院分区：
文献类型：
--
作者：
Adamis, AP;Shima, DT;Miller, JW
目的：为了确定是否血管生成肽血管内皮生长因子（VEGF）所需的视网膜缺血相关的虹膜新生血管在非人灵长类动物。方法：激光视网膜静脉阻塞被用来产生视网膜缺血8只动物（食蟹猴）的16只眼睛。将眼睛随机分配至每隔一天玻璃体内注射中和抗VEGF单克隆抗体或相同同种型的对照单克隆抗体进行治疗。使用标准化分级系统和蒙眼阅片者对连续虹膜荧光素血管造影片进行评估。采用北方印迹法检测视网膜VEGF和胎盘生长因子的表达。在毛细血管内皮细胞增殖试验之前，玻璃体内intravitreal injection.Results：零的8只眼睛接受中和抗VEGF抗体虹膜新生血管形成的抗体的特异性进行了测定。八只对照抗体治疗的眼睛中有五只发生虹膜新血管形成。差异具有统计学意义（P=.03）。玻璃体内注射抗体并不损害缺血性视网膜增加VEGF信使RNA表达的能力。抗VEGF抗体特异性抑制VEGF驱动的毛细血管内皮细胞增殖在vitro.Conclusion：这些数据表明，VEGF是所需的虹膜新生血管在成年非人灵长类动物的眼睛。抑制VEGF是治疗眼部新生血管的一种新的潜在治疗策略。
Objective: To determine if the angiogenic peptide vascular endothelial growth factor (VEGF) is required for retinal ischemia-associated iris neovascularization in a nonhuman primate.Methods: Laser retinal vein occlusion was used to produce retinal ischemia in 16 eyes of eight animals (Macaca fascicularis). Eyes were randomized to treatment every other day with intravitreal injections of either a neutralizing anti-VEGF monoclonal antibody or a control monoclonal antibody of the same isotype. Serial iris fluorescein angiograms were assessed using a standardized grading system and masked readers. Retinal VEGF and placental growth factor expression were assessed by Northern blotting. The specificity of the antibodies was determined in capillary endothelial cell proliferation assays prior to intravitreal injection.Results: Zero of eight eyes receiving the neutralizing anti-VEGF antibodies developed iris neovascularization. Five of eight control antibody-treated eyes developed iris neovascularization. The difference was statistically significant (P=.03). Intravitreal antibody injection did not impair the ability of the ischemic retina to increase VEGF messenger RNA expression. The anti-VEGF antibodies specifically inhibited VEGF-driven capillary endothelial cell proliferation in vitro.Conclusion: These data demonstrate that VEGF is required for iris neovascularization in an adult nonhuman primate eye. The inhibition of VEGF is a new potential therapeutic strategy for the treatment of ocular neovascularization.