Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy
Inducible nitric oxide synthase mediates the change from retinal to vitreal neovascularization in ischemic retinopathy
复制标题
DOI：
10.1172/jci10874
复制
发表时间：
2001-03-01
影响因子：
15.9
通讯作者：
Goureau, O
中科院分区：
文献类型：
--
作者：
Sennlaub, F;Courtois, Y;Goureau, O
玻璃体内。新生血管疾病是全世界失明的主要原因。目前尚不清楚为什么许多视网膜疾病中的新生血管扩散到生理上无血管化的玻璃体，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，我们发现诱导型一氧化氮合酶（iNOS）在缺血性视网膜中表达。使用 iNOS 敲除小鼠和 iNOS 抑制剂 1400W，我们证明 iNOS 表达可抑制无血管视网膜中的局部血管生成，这至少部分是通过 iNOS 表达细胞邻近细胞中 VEGF 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发挥着至关重要的作用，并表明它为通过改善缺氧视网膜的血管化来控制玻璃体新生血管形成提供了理想的靶标。
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.