Resolvin E1 (RX-10001) Reduces Corneal Epithelial Barrier Disruption and Protects Against Goblet Cell Loss in a Murine Model of Dry Eye
Resolvin E1 (RX-10001) Reduces Corneal Epithelial Barrier Disruption and Protects Against Goblet Cell Loss in a Murine Model of Dry Eye
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DOI：
10.1097/ico.0b013e31823f789e
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发表时间：
2012-11-01
期刊：
影响因子：
2.8
通讯作者：
Pflugfelder, Stephen C.
中科院分区：
文献类型：
--
作者：
de Paiva, Cintia S.;Schwartz, C. Eric;Pflugfelder, Stephen C.
目的：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omega-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的有效性，本研究调查了消退素E1在小鼠干眼模型中的有效性。方法：用6至8周龄的C57/B6小鼠全身性东莨菪碱治疗，并暴露于空气通风和低湿度，每天16小时，持续5天，并分配到以下组：未暴露对照、疾病对照、用载体或作为其甲酯前药RX-10005局部递送的RvE 1处理以增强角膜表面渗透。在干燥强制降解诱导时开始处理。通过使用俄勒冈州绿色葡聚糖的角膜渗透性和使用过碘酸-希夫试剂的结膜杯状细胞密度来评估治疗效果。结果：与未经治疗的疾病对照组相比，RvE 1减少了80%的角膜染色增加。结论：RvE 1作为其甲酯前体药物，可改善干眼症小鼠模型角膜染色和杯状细胞密度，提示内源性消退素及其类似物在干眼症治疗中具有潜在的应用价值。
Purpose: 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.Methods: 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.Results: 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.Conclusions: 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.