Bian Fang, Pelegrino Flavia S A, Pflugfelder Stephen C, Volpe Eugene A, Li De-Quan, de Paiva Cintia S
Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4908-18. doi: 10.1167/iovs.15-16631.
To evaluate the effects of dry eye on ocular surface protease activity and sight threatening corneal complications following ocular surface chemical injury.
C57BL/6 mice were subjected to unilateral alkali burn (AB) with or without concomitant dry eye for 2 or 5 days. Mice were observed daily for appearance of corneal perforation. Whole corneas were harvested and lysed for RNA extraction. Quantitative real-time PCR was performed to measure expression of inflammation cytokines, matrix metalloproteinases (MMP). Matrix metalloproteinase-9 activity, gelatinase activity, and myeloperoxidase (MPO) activity were evaluated in corneal lysates. Presence of infiltrating neutrophils was evaluated by immunohistochemistry and flow cytometry.
Eyes subjected to the combined model of AB and dry eye (CM) had 20% sterile corneal perforation rate as soon as 1 day after the initial injury, which increased to 35% by 5 days, delayed wound closure and increased corneal opacity. Increased levels of IL-1β, -6, and MMPs-1, -3, -8, -9, and -13, and chemokine (C-X-C motif) ligand 1 (CSCL1) transcripts were found after 2 days in CM compared with AB corneas. Increased MMP-1, -3, -9, and -13 immunoreactivity and gelatinolytic activity were seen in CM corneas compared with AB. Increased neutrophil infiltration and MPO activity was noted in the CM group compared with AB 2 days post injury.
Desiccating stress worsens outcome of ocular AB, creating a cytokine and protease storm with greater neutrophil infiltration, increasing the risk of corneal perforation.
评估干眼对眼表化学伤后眼表蛋白酶活性及威胁视力的角膜并发症的影响。
对C57BL/6小鼠进行单侧碱烧伤（AB），伴或不伴有干眼，持续2或5天。每天观察小鼠角膜穿孔情况。收集全角膜并裂解以提取RNA。进行定量实时PCR以测量炎症细胞因子、基质金属蛋白酶（MMP）的表达。评估角膜裂解物中基质金属蛋白酶-9活性、明胶酶活性和髓过氧化物酶（MPO）活性。通过免疫组织化学和流式细胞术评估浸润中性粒细胞的存在情况。
遭受碱烧伤和干眼联合模型（CM）的眼睛在初次损伤后1天即有20%的无菌角膜穿孔率，到5天时增至35%，伤口愈合延迟且角膜混浊增加。与AB角膜相比，CM组在2天后发现白细胞介素-1β、-6以及基质金属蛋白酶-1、-3、-8、-9和-13以及趋化因子（C-X-C基序）配体1（CSCL1）转录物水平升高。与AB相比，CM角膜中基质金属蛋白酶-1、-3、-9和-13的免疫反应性和明胶酶活性增加。与损伤后2天的AB组相比，CM组中性粒细胞浸润和MPO活性增加。
干燥应激会使眼表碱烧伤的预后恶化，引发细胞因子和蛋白酶风暴，伴有更多中性粒细胞浸润，增加角膜穿孔风险。
