INSERM, U968, Department of Therapy, Paris, France.
Cornea. 2012 Nov;31(11):1319-29. doi: 10.1097/ICO.0b013e318255a7f8.
Cationic emulsions (CEs), developed as vehicles for lipophilic drugs, have been shown to be safe and effective for the treatment of dry eye. The aim of this study was to investigate the effects of a preservative-free latanoprost 0.005% CE (latanoprost-CE) in in vitro and in vivo models of corneal wound healing.
An in vitro wound was made by scraping through a confluent layer of human corneal epithelial cells. Cytotoxicity, cell migration, and proliferation were analyzed after an exposure to phosphate-buffered saline, CE, latanoprost-CE, 0.02% benzalkonium chloride (0.02%BAK), and Xalatan (latanoprost). In vivo, the recovery and integrity of corneal wound healing were assessed in rat eyes instilled twice a day for 5 days with the above treatments after deepithelialization of the superior cornea.
In vitro wound distances decreased at 2 and 24 hours for human corneal epithelial cells exposed to CE, latanoprost-CE, and phosphate-buffered saline, whereas they progressively increased for 0.02%BAK-treated and latanoprost-treated cells. The greater wound closure was associated with a higher number of Ki67-positive cells. In CE- and latanoprost-CE-treated rats, reepithelialization of the cornea was enhanced, restoring normal appearance and function. In contrast, 0.02%BAK or latanoprost delayed corneal healing, induced inflammation, and decreased MUC5-AC expression.
Both models effectively evaluated the cytotoxicity and dynamic recovery of corneal wound healing, and their correlation supports the potential of the in vitro model as a reliable alternative to in vivo ocular toxicity tests. Both models demonstrated that in the face of corneal injury, CEs favored corneal healing, whereas BAK was deleterious.
阳离子乳液（CE）作为亲脂性药物的载体，已被证明对干眼症的治疗安全有效。本研究旨在研究不含防腐剂的拉坦前列素 0.005%CE（拉坦前列素-CE）在体外和体内角膜伤口愈合模型中的作用。
通过刮除铺满的人角膜上皮细胞层来制造体外伤口。在用磷酸盐缓冲盐水、CE、拉坦前列素-CE、0.02%苯扎氯铵（0.02%BAK）和 Xalatan（拉坦前列素）处理后，分析细胞毒性、细胞迁移和增殖。在体内，通过对角膜上皮细胞进行深度去上皮化后，每天两次滴注上述治疗药物，连续 5 天，评估大鼠眼角膜伤口愈合的恢复和完整性。
在暴露于 CE、拉坦前列素-CE 和磷酸盐缓冲盐水的人角膜上皮细胞中，2 小时和 24 小时的体外伤口距离减小，而暴露于 0.02%BAK 处理和拉坦前列素处理的细胞的伤口距离逐渐增加。更大的伤口闭合与更多的 Ki67 阳性细胞相关。在 CE 和拉坦前列素-CE 处理的大鼠中，角膜的重新上皮化得到增强，恢复了正常的外观和功能。相比之下，0.02%BAK 或拉坦前列素延迟了角膜愈合，引起炎症并降低了 MUC5-AC 的表达。
两种模型均有效地评估了角膜伤口愈合的细胞毒性和动态恢复，并且它们的相关性支持体外模型作为体内眼毒性试验的可靠替代方法的潜力。两种模型均表明，在面对角膜损伤时，CE 有利于角膜愈合，而 BAK 则有害。
