Toxicity of Topical Antifungal Agents to Stratified Human Cultivated Corneal Epithelial Sheets
Toxicity of Topical Antifungal Agents to Stratified Human Cultivated Corneal Epithelial Sheets
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DOI：
10.1089/jop.2014.0044
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发表时间：
2014-12-01
影响因子：
2.3
通讯作者：
Amano, Shiro
中科院分区：
文献类型：
--
作者：
Kimakura, Mikiko;Usui, Tomohiko;Amano, Shiro
目的：长期使用局部抗真菌药物可能损害角膜上皮的完整性。在这里，我们使用人分层角膜上皮的体外模型来比较4种不同的抗真菌滴眼液的眼部毒性。方法：人角膜上皮细胞片在含0.1%米卡芬金、1%伏立康唑、5%海马霉素、0.1%两性霉素B或对照（生理盐水或5%葡萄糖）的无血清培养基中培养。分别用WST-1法和羧基荧光素通透性法测定细胞活力和屏障功能。通过伤口愈合实验测量细胞迁移。结果：WST-1试验和羧基荧光素通透性试验显示两性霉素B毒性最大，其次为吡马西林、米卡芬净和伏立康唑。在伤口愈合试验中，细胞迁移的减少顺序如下：两性霉素B、匹马西林、米卡芬净和伏立康唑。结论：米卡芬金和伏立康唑对角膜上皮的毒性最小。药物处方不仅要考虑真菌种类和敏感性，还要考虑眼毒性和治疗阶段。
Purpose: Prolonged use of topical antifungal agents may compromise corneal epithelial integrity. Here, we used an in vitro model of human stratified corneal epithelium to compare the ocular toxicity profiles of 4 different antifungal eye drops.Methods: Human corneal epithelial cell sheets were cultured in a serum-free medium containing 0.1% micafungin, 1% voriconazole, 5% pimaricin, 0.1% amphotericin B, or controls (saline or 5% glucose). Cell viability and barrier function were measured by WST-1 assay and carboxyfluorescein permeability assay, respectively. Cell migration was measured on a wound healing assay.Results: WST-1 assay and carboxyfluorescein permeability assay revealed that amphotericin B was the most toxic drug, followed by pimaricin, micafungin, and voriconazole. Cell migration on a wound healing assay was decreased in the following order, amphotericin B, pimaricin, micafungin, and voriconazole.Conclusions: Topical micafungin and voriconazole appeared to be the least toxic to the corneal epithelium. Drug prescription should consider not only fungal species and susceptibility but also ocular toxicity and stage of treatment.