Sennlaub F, Courtois Y, Goureau O
Développement, Vieillissement, et Pathologie de la Rétine, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 450, Association Claude Bernard, 29 rue Wilhem, 75016 Paris, France.
J Clin Invest. 2001 Mar;107(6):717-25. doi: 10.1172/JCI10874.
Intravitreal neovascular diseases are a major cause of blindness worldwide. It remains unclear why neovessels in many retinal diseases spread into the physiologically nonvascularized vitreous rather than into the ischemic retinal areas, where the angiogenic factors are released. Here we show that inducible nitric oxide synthase (iNOS) is expressed in the ischemic retina. Using iNOS knockout mice and the iNOS inhibitor 1400W, we demonstrate that iNOS expression inhibits angiogenesis locally in the avascular retina, mediated at least in part by a downregulation of VEGF receptor 2 (VEGFR2) in cells adjacent to iNOS-expressing cells. At the same time, pathological intravitreal neovascularization is considerably stronger in iNOS-expressing animals. These findings demonstrate that iNOS plays a crucial role in retinal neovascular disease and show that it offers an ideal target for the control of vitreal neovascularization through improvement of the vascularization of the hypoxic retina.
玻璃体内新生血管疾病是全球失明的主要原因。目前尚不清楚为何许多视网膜疾病中的新生血管会扩散到生理上无血管的玻璃体中，而不是扩散到释放血管生成因子的缺血性视网膜区域。在这里，我们表明诱导型一氧化氮合酶（iNOS）在缺血性视网膜中表达。使用iNOS基因敲除小鼠和iNOS抑制剂1400W，我们证明iNOS的表达在无血管视网膜中局部抑制血管生成，这至少部分是由iNOS表达细胞附近细胞中血管内皮生长因子受体2（VEGFR2）的下调介导的。同时，在表达iNOS的动物中，病理性玻璃体内新生血管形成明显更强。这些发现表明iNOS在视网膜新生血管疾病中起关键作用，并表明它是通过改善缺氧视网膜的血管化来控制玻璃体内新生血管形成的理想靶点。
