School of Optometry, University of California, Berkeley, CA, USA.
School of Optometry, University of California, Berkeley, CA, USA; Vision Science Program, University of California, Berkeley, CA, USA.
Exp Eye Res. 2019 Feb;179:1-7. doi: 10.1016/j.exer.2018.10.010. Epub 2018 Oct 19.
Research with animal models of Pseudomonas aeruginosa keratitis has shown that use of a topical corticosteroid alone against an established infection can significantly increase the number of colonizing bacteria or worsen clinical disease. Moreover, retrospective analysis has suggested that corticosteroid use in humans is associated with an increased risk of keratitis in eyes with pre-existing disease. Thus, while corticosteroids are often used to reduce ocular inflammation in the absence of infection, the risk of opportunistic infection remains a concern. However, the effect of corticosteroids on the intrinsic barrier function of uninfected corneas is unknown. Here, we tested if short-term topical corticosteroid treatment of an uninfected murine cornea would increase susceptibility to P. aeruginosa colonization or infection after epithelial injury. Topical prednisolone acetate (1%) was administered to one eye of C57BL/6 mice three times a day for 3 days; control eyes were treated with sterile PBS. Prior to inoculation with a cytotoxic P. aeruginosa corneal isolate strain 6206, corneas were subject to superficial-injury by tissue paper blotting, or scratch-injured followed by 12 h of healing. Previously we have shown that blotting renders mouse corneas susceptible to P. aeruginosa adhesion, but not infection, while 12 h healing reduces susceptibility to infection after scratching. Corneas were evaluated at 48 h for bacterial colonization and microbial keratitis (MK). To monitor impact on wound healing, corneal integrity was examined by fluorescein staining immediately after scarification and after 12 h healing. For both the tissue paper blotting and scratch-injury models, there was no significant difference in P. aeruginosa colonization at 48 h between corticosteroid-pretreated eyes and controls. With the blotting model, one case of MK was observed in a control (PBS-pretreated) cornea; none in corticosteroid-pretreated corneas. With the 12 h healing model, MK occurred in 6 of 17 corticosteroid-pretreated eyes versus 2 of 17 controls, a difference not statistically significant. Corticosteroid-pretreated eyes showed greater fluorescein staining 12 h after scarification injury, but this did not coincide with increased colonization or MK. Together, these data show that short-term topical corticosteroid therapy on an uninfected murine cornea does not necessarily enhance its susceptibility to P. aeruginosa colonization or infection after injury, even when it induces fluorescein staining.
铜绿假单胞菌角膜炎的动物模型研究表明，在已建立的感染中单独使用局部皮质类固醇可能会显著增加定植细菌的数量或使临床疾病恶化。此外，回顾性分析表明，皮质类固醇在人类中的使用与先前存在疾病的眼睛中角膜炎的风险增加有关。因此，尽管皮质类固醇通常用于在没有感染的情况下减轻眼部炎症，但机会性感染的风险仍然是一个问题。然而，皮质类固醇对未感染角膜的固有屏障功能的影响尚不清楚。在这里，我们测试了短期局部皮质类固醇治疗未感染的小鼠角膜是否会增加上皮损伤后铜绿假单胞菌定植或感染的易感性。将醋酸泼尼松龙（1%）每天三次施用于 C57BL/6 小鼠的一只眼睛，持续 3 天；对照眼用无菌 PBS 处理。在用细胞毒性铜绿假单胞菌角膜分离株 6206 接种之前，通过纸巾擦拭对角膜进行浅表损伤，或划痕损伤后愈合 12 小时。之前我们已经表明，擦拭使小鼠角膜易受铜绿假单胞菌粘附，但不易受感染，而 12 小时的愈合会降低划痕后感染的易感性。在 48 小时时，对细菌定植和微生物角膜炎（MK）进行评估。为了监测对伤口愈合的影响，在划痕后立即和 12 小时愈合后通过荧光素染色检查角膜完整性。对于纸巾擦拭和划痕损伤模型，在皮质类固醇预处理眼和对照眼之间，48 小时时铜绿假单胞菌定植没有显著差异。在擦拭模型中，对照（PBS 预处理）角膜中有一例 MK；皮质类固醇预处理角膜中无一例。在 12 小时愈合模型中，皮质类固醇预处理的眼睛中有 6 只发生了 MK，而对照的眼睛中有 2 只发生了 MK，差异无统计学意义。划痕损伤后 12 小时，皮质类固醇预处理的眼睛中荧光素染色更严重，但这并没有增加定植或 MK。总的来说，这些数据表明，在未感染的小鼠角膜上进行短期局部皮质类固醇治疗不一定会增加其在受伤后对铜绿假单胞菌定植或感染的易感性，即使它会诱导荧光素染色。
