Medical College, Qingdao University, Qingdao, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao, China.
Exp Eye Res. 2020 Jun;195:108048. doi: 10.1016/j.exer.2020.108048. Epub 2020 May 4.
Tissue injury causes the secretion of stress hormone catecholamine and increases susceptibility to opportunistic infection. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that is a leading cause of microbial keratitis usually associated with ocular injury or contact lens wear. However, the effect of catecholamine on P. aeruginosa induced corneal infection is unknown. Here, we test if norepinephrine (NE) would promote the progression of P. aeruginosa keratitis in mice. Adult C57BL/6 mouse corneas were scarified and then inoculated with P. aeruginosa. The content of NE was elevated in corneas after scarification and inoculation with P. aeruginosa. Then, exogenous NE was applied to the infected corneas at 24 h after inoculation; control eyes were treated with sterile saline. Topical application of NE aggravated the severity of P. aeruginosa keratitis, accompanied with the increase of clinical score, bacterial load, pathological changes, neutrophils infiltration, bacterial virulence factors and proinflammatory factors levels. In order to further verify the role of NE, N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4), a neurotoxin selected to deplete NE, was injected subconjunctivally 12 h before scarification. Pre-depletion of local NE by DSP-4 significantly alleviated the severity of corneal infection. Moreover, NE was also confirmed to increase the bacterial growth and the expression of virulence factors gene in vitro. Together, these data showed that increased corneal NE content facilitated the progression of P. aeruginosa keratitis in mice by amplifying host excessive inflammatory response and bacterial virulence. Therefore, targeting NE may provide a potential strategy for the treatment of P. aeruginosa keratitis.
组织损伤会导致应激激素儿茶酚胺的分泌增加，并增加机会性感染的易感性。铜绿假单胞菌（P. aeruginosa）是一种机会致病菌，通常与眼部损伤或隐形眼镜佩戴有关，是微生物角膜炎的主要致病原因。然而，儿茶酚胺对铜绿假单胞菌诱导的角膜感染的影响尚不清楚。在这里，我们测试去甲肾上腺素（NE）是否会促进小鼠铜绿假单胞菌角膜炎的进展。成年 C57BL/6 小鼠角膜划痕，然后接种铜绿假单胞菌。划痕和接种铜绿假单胞菌后，角膜中的 NE 含量升高。然后，在接种后 24 小时将外源性 NE 应用于感染的角膜；对照眼用无菌生理盐水处理。局部应用 NE 加重了铜绿假单胞菌角膜炎的严重程度，伴随着临床评分、细菌负荷、病理变化、中性粒细胞浸润、细菌毒力因子和促炎因子水平的增加。为了进一步验证 NE 的作用，在划痕前 12 小时，通过结膜下注射 N-（2-氯乙基）-N-乙基-2-溴苯甲胺盐酸盐（DSP-4），一种选择用于耗尽 NE 的神经毒素。DSP-4 预先耗尽局部 NE 可显著减轻角膜感染的严重程度。此外，NE 还被证实可增加体外细菌生长和毒力因子基因的表达。总之，这些数据表明，角膜 NE 含量的增加通过放大宿主过度炎症反应和细菌毒力，促进了小鼠铜绿假单胞菌角膜炎的进展。因此，针对 NE 可能为治疗铜绿假单胞菌角膜炎提供一种潜在策略。
