Parstatin Suppresses Ocular Neovascularization and Inflammation
Parstatin Suppresses Ocular Neovascularization and Inflammation
复制标题
DOI：
10.1167/iovs.10-5576
复制
发表时间：
2010-11-01
影响因子：
4.4
通讯作者：
Tsopanoglou, Nikos E.
中科院分区：
文献类型：
--
作者：
Huang, Hu;Vasilakis, Panagiotis;Tsopanoglou, Nikos E.
目的。Parstatin是一种蛋白水解性裂解激活PAR1受体而形成的41肽。作者最近发现，parstatin是一种有效的血管生成抑制剂。本研究的目的是评价parstatin对眼部新生血管的治疗作用。方法：用激光诱导Bruch膜破裂的方法建立小鼠脉络膜新生血管模型，并在FITC-葡聚糖灌流14天后进行评估。新生小鼠在出生后第7天暴露于75%O-2中5天，然后置于室内空气中5天，以建立氧诱导的视网膜新生血管。用抗小鼠PECAM-1染色后对P17进行检测。玻璃体腔内给药后检测parstatin的作用。在化学烧伤诱导的角膜新生血管形成后7天，观察结膜下注射parstatin对大鼠角膜新生血管和炎症的影响。结果Parstatin能有效地抑制脉络膜新生血管，IC50约为3微克，10微克时最大抑制率为59%，3微克时最大抑制率为60%，10微克和30微克剂量对新生视网膜有毒性作用。结膜下注射parstatin抑制角膜新生血管，最有效剂量为200 mU，抑制率为59%。此外，parstatin显著抑制角膜炎症和血管内皮细胞生长因子诱导的视网膜白细胞停滞。在所有被测试的模型中，杂乱的parstatin没有任何明显的效果。结论：parstatin是一种有效的抗新生血管药物，可能在治疗血管生成相关的眼部疾病方面具有临床潜力。(投资眼科VS科学。地址：10.1167/iovs.10-5576
PURPOSE. Parstatin is a 41-mer peptide formed by proteolytic cleavage on activation of the PAR1 receptor. The authors recently showed that parstatin is a potent inhibitor of angiogenesis. The purpose of the present study was to evaluate the therapeutic effect of parstatin on ocular neovascularization.METHODS. Choroidal neovascularization was generated in mice using laser-induced rupture of Bruch's membrane and was assessed after 14 days after perfusion of FITC-dextran. Oxygen-induced retinal neovascularization was established in neonatal mice by exposing them to 75% O-2 at postnatal day (P) 7 for 5 days and then placing them in room air for 5 days. Evaluation was performed on P17 after staining with anti-mouse PECAM-1. The effect of parstatin was tested after intravitreal administration. The effects of subconjunctival-injected parstatin on corneal neovascularization and inflammation in rats were assessed 7 days after chemical burn-induced corneal neovascularization. Retinal leukostasis in mice was assessed after perfusion with FITC-conjugated concanavalin A.RESULTS. Parstatin potently inhibited choroidal neovascularization with an IC50 of approximately 3 mu g and a maximum inhibition of 59% at 10 mu g. Parstatin suppressed retinal neovascularization with maximum inhibition of 60% at 3 mu g. Ten-microgram and 30-mu g doses appeared to be toxic to the neonatal retina. Subconjunctival parstatin inhibited corneal neovascularization, with 200 mu g the most effective dose (59% inhibition). In addition, parstatin significantly inhibited corneal inflammation and VEGF-induced retinal leukostasis. In all models tested, scrambled parstatin was without any significant effect.CONCLUSIONS. Parstatin is a potent antiangiogenic agent of ocular neovascularization and may have clinical potential in the treatment of angiogenesis-related ocular disorders. (Invest Ophthalmol Vis Sci. 2010;51:5825-5832) DOI:10.1167/iovs.10-5576