Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
Clin Exp Ophthalmol. 2012 Jan-Feb;40(1):e58-66. doi: 10.1111/j.1442-9071.2011.02656.x. Epub 2011 Sep 28.
Caveolin-1 expression correlates with the permeability of endothelial barriers and angiogenesis. However, the role of caveolin-1 in retinal neovascularization remains unknown. We evaluated the effect of caveolin-1 on the blood-retina barrier and retinal neovascularization in a murine model of oxygen-induced retinopathy.
Starting at postnatal day 7, mice were exposed to 75 ± 5% oxygen for 5 days and then returned to room air conditions to induce retinal neovascularization. Effects on blood-retina barrier were evaluated by Western blot analysis of extravasated albumin in the retina. Retinal neovascularization morphology was studied by fluorescence angiography and was quantified by counts of the endothelial nuclei that protruded into the vitreous cavity. Reverse transcription-polymerase chain reaction and Western blot analysis was used to examine retinal expression levels of caveolin-1. siRNA against caveolin-1 was injected intravitreally in the oxygen-induced retinopathy models. Effects on caveolin-1 mRNA and protein, and retinal neovascularization were assessed as described above.
Caveolin-1 expression was found to increase during hypoxia and overexpression of caveolin-1 correlated with the appearance of extravascular albumin. Caveolin-1 siRNA reduced caveolin-1 mRNA and protein levels by 47.94% and 54.76%, respectively. Furthermore, caveolin-1 siRNA inhibition reduced retinal neovascularization by 51.3% and reduced albumin leakage by 56.32%.
Caveolin-1 may play an important role in induction of retinal neovascularization. SiRNA against caveolin-1 can inhibit experimental retinal hyperpermeability and neovascularization. Therefore, the inhibition of caveolin-1 may be a powerful and novel therapeutic tool for the treatment of ischaemia-induced retinal diseases.
窖蛋白-1 的表达与内皮屏障的通透性和血管生成有关。然而，窖蛋白-1 在视网膜新生血管形成中的作用尚不清楚。我们在氧诱导的视网膜病变的小鼠模型中评估了窖蛋白-1 对血视网膜屏障和视网膜新生血管形成的影响。
从出生后第 7 天开始，将小鼠暴露于 75±5%的氧气中 5 天，然后返回室内空气条件下诱导视网膜新生血管形成。通过Western blot 分析视网膜中渗出的白蛋白来评估血视网膜屏障的影响。通过荧光血管造影研究视网膜新生血管形成的形态，并通过计数突入玻璃体腔的内皮核来量化。使用逆转录-聚合酶链反应和 Western blot 分析来检测窖蛋白-1 在视网膜中的表达水平。将窖蛋白-1 的 siRNA 眼内注射到氧诱导的视网膜病变模型中。如上所述，评估对窖蛋白-1 mRNA 和蛋白以及视网膜新生血管形成的影响。
发现窖蛋白-1 在缺氧时表达增加，并且窖蛋白-1 的过表达与血管外白蛋白的出现相关。窖蛋白-1 siRNA 使窖蛋白-1 mRNA 和蛋白水平分别降低了 47.94%和 54.76%。此外，窖蛋白-1 siRNA 抑制使视网膜新生血管形成减少了 51.3%，白蛋白渗漏减少了 56.32%。
窖蛋白-1 可能在诱导视网膜新生血管形成中起重要作用。窖蛋白-1 的 siRNA 可抑制实验性视网膜高通透性和新生血管形成。因此，抑制窖蛋白-1 可能是治疗缺血性视网膜疾病的一种强大而新颖的治疗工具。
