Impact of topical corticosteroid pretreatment on susceptibility of the injured murine cornea to Pseudomonas aeruginosa colonization and infection.
Impact of topical corticosteroid pretreatment on susceptibility of the injured murine cornea to Pseudomonas aeruginosa colonization and infection.
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DOI：
10.1016/j.exer.2018.10.010
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发表时间：
2019-03
影响因子：
3.4
通讯作者：
Fleiszig SMJ
中科院分区：
文献类型：
--
作者：
Wu YT;Truong TN;Tam C;Mendoza MN;Zhu L;Evans DJ;Fleiszig SMJ
对铜绿假单胞菌角膜炎动物模型的研究表明，单独使用局部皮质类固醇来对抗已确定的感染会显着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，人类使用皮质类固醇与患有既往疾病的眼睛患角膜炎的风险增加有关。因此，虽然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令人担忧。然而，皮质类固醇对未感染角膜内在屏障功能的影响尚不清楚。在这里，我们测试了未感染的小鼠角膜的短期局部皮质类固醇治疗是否会增加上皮损伤后对铜绿假单胞菌定植或感染的易感性。对 C57BL/6 小鼠的一只眼睛局部施用醋酸泼尼松龙 (1%)，每天 3 次，持续 3 天；对照眼睛用无菌PBS处理。在接种细胞毒性铜绿假单胞菌角膜分离菌株 6206 之前，通过薄纸吸印对角膜进行表面损伤，或进行划伤，然后进行 12 小时的愈合。之前我们已经证明，印迹使小鼠角膜容易受到铜绿假单胞菌粘附，但不会受到感染，而12小时愈合会降低抓伤后感染的易感性。 48 小时评估角膜的细菌定植和微生物角膜炎 (MK)。为了监测对伤口愈合的影响，在划痕后和愈合 12 小时后立即通过荧光素染色检查角膜完整性。对于纸巾印迹和划痕损伤模型，48小时时皮质类固醇预处理的眼睛和对照组之间的铜绿假单胞菌定植没有显着差异。通过印迹模型，在对照（PBS 预处理）角膜中观察到 1 例 MK；在皮质类固醇预处理的角膜中没有。在 12 小时愈合模型中，17 只经过皮质类固醇预处理的眼睛中有 6 只发生了 MK，而 17 只对照眼中有 2 只发生了 MK，差异无统计学意义。划痕损伤后 12 小时，经过皮质类固醇预处理的眼睛显示出更高的荧光素染色，但这与定植或 MK 的增加并不相符。总之，这些数据表明，对未感染的小鼠角膜进行短期局部皮质类固醇治疗并不一定会增强其对铜绿假单胞菌定植或损伤后感染的易感性，即使它诱导荧光素染色。
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.
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影响因子：
4.2
作者：
Evans DJ;Fleiszig SM
通讯作者：
Fleiszig SM
影响因子：
4.6
作者：
Metruccio MME;Tam C;Evans DJ;Xie AL;Stern ME;Fleiszig SMJ
通讯作者：
Fleiszig SMJ
影响因子：
17.8
作者：
Ljubimov AV;Saghizadeh M
通讯作者：
Saghizadeh M
影响因子：
8.1
作者：
Borkar, Durga S.;Fleiszig, Suzanne M. J.;Leong, Chelsia;Lalitha, Prajna;Srinivasan, Muthiah;Ghanekar, Avanti A.;Tam, Connie;Li, Wing Y.;Zegans, Michael E.;McLeod, Stephen D.;Lietman, Thomas M.;Acharya, Nisha R.
通讯作者：
Acharya, Nisha R.
影响因子：
4.4
作者：
Lee, EJ;Evans, DJ;Fleiszig, SMJ
通讯作者：
Fleiszig, SMJ