Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier
Angiopoietin 1 inhibits ocular neovascularization and breakdown of the blood-retinal barrier
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DOI：
10.1038/sj.gt.3302230
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发表时间：
2004-05-01
期刊：
影响因子：
5.1
通讯作者：
Campochiaro, PA
中科院分区：
文献类型：
--
作者：
Nambu, H;Nambu, R;Campochiaro, PA
一些视网膜和脉络膜疾病可以通过眼内递送基因来治疗，这些基因的产物可以对抗或中和作为疾病一部分而发生的异常基因表达。然而，在考虑转基因之前，有必要彻底研究其表达在正常和患病眼睛中的影响。实现这一目标的有效方法是将组织特异性启动子与转基因小鼠中的诱导型启动子系统相结合。在本研究中，我们使用这种方法来评估血管生成素-1 (Ang1) 异位表达对正常眼和眼部新生血管形成的影响。普遍存在Ang1诱导表达（或在视网膜中特异性表达）的成年小鼠表现正常，视网膜或脉络膜血管或通过视网膜电图检查评估的视网膜功能没有可识别的变化。患有严重视网膜缺血的眼睛或患有布鲁赫膜破裂的眼睛中Ang1表达增加，分别显着抑制视网膜或脉络膜新生血管的发展。这种对眼部新生血管形成的抑制特别有趣且值得注意，因为皮肤中 Ang1 的过度表达会刺激新生血管形成。 Ang1 还显着降低 VEGF 诱导的视网膜血管通透性。这些数据表明，ang1的眼内递送具有治疗眼部新生血管和黄斑水肿的潜力。
Several retinal and choroidal diseases are potentially treatable by intraocular delivery of genes whose products may counter or neutralize abnormal gene expression that occurs as part of the diseases. However, prior to considering a transgene, it is necessary to thoroughly investigate the effects of its expression in normal and diseased eyes. An efficient way to do this is to combine tissue-specific promoters with inducible promoter systems in transgenic mice. In this study, we used this approach to evaluate the effects of ectopic expression of angiopoietin-1 (Ang1) in normal eyes and those with ocular neovascularization. Adult mice with induced expression of Ang1 ubiquitously, or specifically in the retina, appeared normal and had no identifiable changes in retinal or choroidal blood vessels or in retinal function as assessed by electroretinography. Increased expression of Ang1 in eyes with severe retinal ischemia or in eyes with rupture of Bruch's membrane significantly suppressed the development of retinal or choroidal neovascularization, respectively. This inhibition of ocular neovascularization is particularly interesting and noteworthy, because overexpression of Ang1 in skin stimulates neovascularization. Ang1 also significantly reduced VEGF-induced retinal vascular permeability. These data suggest that intraocular delivery of ang1 has potential for treatment of ocular neovascularization and macular edema.