Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Cornea. 2012 Nov;31(11):1299-303. doi: 10.1097/ICO.0b013e31823f789e.
Resolvin E1 (RvE1; RX-10001) belongs to a new class of endogenous immunoregulating mediators, originally identified as a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid. Based on its proven efficacy in models of chronic inflammation, this study investigated the efficacy of resolvin E1 in a murine model of dry eye.
C57/B6 mice, aged 6 to 8 weeks, were treated with systemic scopolamine and exposed to air draft and low humidity for 16 hours/day for 5 days and allocated to the following groups: unexposed controls, disease controls, treatment with vehicle or RvE1 delivered topically as its methyl ester prodrug, RX-10005, to enhance corneal surface penetration. Treatment was initiated at the time of desiccating stress induction. Treatment efficacy was assessed by corneal permeability using Oregon Green Dextran and by conjunctival goblet cell density using periodic acid-Schiff reagent.
RvE1 reduced the increase in corneal staining by 80% compared with untreated disease controls. Goblet cell density was reduced by 20% in disease controls but fully maintained in the group receiving RvE1.
RvE1, delivered as its methyl ester prodrug, improved the outcome measures of corneal staining and goblet cell density in this murine model of dry eye, indicating the potential utility of endogenous resolvins and resolvin analogues in the treatment of dry eye.
Resolvin E1(RvE1;RX-10001)属于一类新的内源性免疫调节介质,最初被鉴定为ω-3 多不饱和脂肪酸,二十碳五烯酸的代谢产物。基于其在慢性炎症模型中已证实的功效,本研究调查了 Resolvin E1 在干眼症小鼠模型中的疗效。
6 至 8 周龄 C57/B6 小鼠接受全身东莨菪碱治疗,并每天暴露于空气气流和低湿度环境中 16 小时,共 5 天,并分为以下几组:未暴露对照、疾病对照、给予载体或通过局部施用其甲酯前药 RX-10005 给予 RvE1 的治疗组,以增强角膜表面穿透性。在干燥应激诱导时开始治疗。通过 Oregon Green Dextran 评估角膜通透性,通过过碘酸希夫试剂评估结膜杯状细胞密度来评估治疗效果。
与未治疗的疾病对照组相比,RvE1 使角膜染色增加减少了 80%。疾病对照组的杯状细胞密度降低了 20%,但接受 RvE1 治疗的组完全维持。
以甲酯前药形式给予的 RvE1 改善了干眼症小鼠模型的角膜染色和杯状细胞密度等测量指标,表明内源性 Resolvin 及其类似物在干眼症治疗中的潜在应用价值。