Ju Brent, Guo Owen, Benissan-Messan Dathe Z, Shawver McKinley H, Chen Peng, Geng Bingchuan, Wei Siqi, Yaron Jordan R, Lucas Alexandra R, Zhu Hua
Division of Cardiac Surgery, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States.
Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Tempe, AZ, United States.
Front Cardiovasc Med. 2021 Jun 4;8:649124. doi: 10.3389/fcvm.2021.649124. eCollection 2021.
Chemical corneal injuries carry a high morbidity and commonly lead to visual impairment. Here, we investigate the role of Serp-1, a serine protease inhibitor, in corneal wound healing. An alkaline-induced corneal injury was induced in 14 mice. Following injury, five mice received daily topical saline application while nine mice received Serp-1 100 μL topically combined with a daily subcutaneous injection of 100 ng/gram body weight of Serp-1. Corneal damage was monitored daily through fluorescein staining and imaging. Cross sectional corneal H&E staining were obtained. CD31 was used as marker for neovascularization. Serp-1 facilitates corneal wound healing by reducing fibrosis and neovascularization while mitigating inflammatory cell infiltration with no noticeable harm related to its application. Serp-1 effectively mitigates inflammation, decreases fibrosis, and reduce neovascularization in a murine model of corneal injury without affecting other organs. Our study provides preclinical data for topical application of Serp-1 to treat corneal wounds.
化学性角膜损伤发病率高,常导致视力损害。在此,我们研究丝氨酸蛋白酶抑制剂Serp-1在角膜伤口愈合中的作用。对14只小鼠造成碱性诱导的角膜损伤。损伤后,5只小鼠每日局部应用生理盐水,而9只小鼠局部应用100 μL Serp-1并每日皮下注射100 ng/克体重的Serp-1。通过荧光素染色和成像每日监测角膜损伤情况。获取角膜横断面苏木精-伊红染色。CD31用作新生血管形成的标志物。Serp-1通过减少纤维化和新生血管形成促进角膜伤口愈合,同时减轻炎症细胞浸润,且其应用未造成明显损害。在角膜损伤小鼠模型中,Serp-1可有效减轻炎症、减少纤维化并降低新生血管形成,且不影响其他器官。我们的研究为局部应用Serp-1治疗角膜伤口提供了临床前数据。