Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy
Oligodeoxynucleotides inhibit retinal neovascularization in a murine model of proliferative retinopathy
复制标题
DOI：
10.1073/pnas.93.10.4851
复制
发表时间：
1996-05-14
影响因子：
11.1
通讯作者：
Smith, LEH
中科院分区：
文献类型：
--
作者：
Robinson, GS;Pierce, EA;Smith, LEH
以视网膜新生血管为特征的疾病是全世界视力丧失的主要原因之一。缺氧刺激下血管内皮生长因子（VEGF）的表达与新血管的增殖有关，我们研究了在小鼠增殖性视网膜病变模型中使用反义硫代寡脱氧核苷酸抑制小鼠VEGF以抑制视网膜新生血管和VEGF合成。与对照组相比，在增殖性视网膜病变发病前玻璃体内注射两种不同的反义硫代寡脱氧核苷酸平均减少了25%和31%的新血管生长。这种抑制作用依赖于反义硫代寡脱氧核苷酸的浓度，并导致VEGF蛋白水平降低40-66%，这是通过Western blot分析确定的。对照（意义上的，非特异性的）硫代寡脱氧核苷酸没有引起视网膜新生血管或VEGF蛋白水平的显著降低。这些数据进一步证实了VEGF在缺血诱导的增生性视网膜病变中的基本作用，以及反义硫代寡脱氧核苷酸的潜在治疗用途。
Diseases characterized by retinal neovascularization are among the principal causes of visual loss worldwide. The hypoxia-stimulated expression of vascular endothelial growth factor (VEGF) has been implicated in the proliferation of new blood vessels, We have investigated the use of antisense phosphorothioate oligodeoxynucleotides against murine VEGF to inhibit retinal neovascularization and VEGF synthesis in a murine model of proliferative retinopathy. Intravitreal injections of two different antisense phosphorothioate oligodeoxynucleotides prior to the onset of proliferative retinopathy reduced new blood vessel growth a mean of 25 and 31% compared with controls. This inhibition was dependent on the concentration of antisense phosphorothioate oligodeoxynucleotides and resulted in a 40-66% reduction in the level of VEGF protein, as determined by Western blot analysis. Control (sense, nonspecific) phosphorothioate oligodeoxynucleotides did not cause a significant reduction in retinal neovascularization or VEGF protein levels. These data further establish a fundamental role for VEGF expression in ischemia-induced proliferative retinopathies and a potential therapeutic use for antisense phosphorothioate oligodeoxynucleotides.