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对长期佩戴隐形眼镜者的人眼角膜基质进行蛋白质组学分析,揭示了炎症反应的激活。

Proteomic profiling of human corneal stroma from long-term contact lens wearers reveals activation of inflammatory responses.

机构信息

Department of Ophthalmology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Department of Ophthalmology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

出版信息

Cont Lens Anterior Eye. 2023 Jun;46(3):101820. doi: 10.1016/j.clae.2023.101820. Epub 2023 Feb 10.

Abstract

PURPOSE

To investigate the association between proteomic changes and potential pathogenesis in the human cornea with respect to the duration of wearing soft contact lenses (SCLs).

METHODS

A total of 96 corneal stroma samples, obtained via small incision lenticule extraction (SMILE), were equally grouped according to the duration of wearing SCL: 0Y, did not wear SCL; 5Y, wore SCL for<5 years; 5-10Y, wore SCL for 5-10 years; O10Y, wore SCL for>10 years. Liquid chromatography-tandem mass spectrometry was used to identify and quantify protein profiles in the corneal stroma. Expression levels of CO1A1, CO4A1, NFKB1, and IL6RB were determined using western blot and immunohistochemistry analysis.

RESULTS

This study quantified a total of 5,668 proteins across samples and identified 2,379 differentially expressed proteins (DEPs) with significantly increased abundance in the three SCL-wearing groups compared with that in the non-SCL-wearing group. Compared with those in the 0Y group, the molecular functions of DEPs in the 5Y, 5-10Y, and O10Y groups were mainly related to translation regulator activity, antigen binding, peptidase inhibitor activity, participation in extracellular matrix (ECM) production, complement activation, and inflammatory responses. Pathway enrichment analysis of DEPs showed that the sphingolipid, phosphatidylinositol 3-kinase-protein kinase B, and hypoxia-inducible factor-1 signaling pathways were activated in the human corneal stroma after long-term SCL use.

CONCLUSIONS

Inflammation-related proteomic components in human corneal stroma increased after long-term use of SCL and may act as an essential factor in the molecular pathogenesis of corneal stroma damage.

摘要

目的

探讨与软性隐形眼镜(SCL)佩戴时间相关的人眼角膜蛋白质组变化与潜在发病机制之间的关系。

方法

共96 例角膜基质样本取自微创性准分子激光角膜微透镜切除术(SMILE),根据佩戴 SCL 的时间长短将其均分为 4 组:0Y 组,未佩戴 SCL;5Y 组,佩戴 SCL<5 年;5-10Y 组,佩戴 SCL5-10 年;O10Y 组,佩戴 SCL>10 年。采用液相色谱-串联质谱技术鉴定和定量分析角膜基质中的蛋白质谱。采用 Western blot 和免疫组织化学分析检测 CO1A1、CO4A1、NFKB1 和 IL6RB 的表达水平。

结果

本研究共定量分析了 5668 种蛋白质,发现与不佩戴 SCL 组相比,3 个 SCL 佩戴组中共有 2379 种差异表达蛋白(DEPs)的丰度显著增加。与 0Y 组相比,5Y、5-10Y 和 O10Y 组 DEPs 的分子功能主要与翻译调节因子活性、抗原结合、肽酶抑制剂活性、参与细胞外基质(ECM)生成、补体激活和炎症反应有关。DEPs 的通路富集分析显示,长期佩戴 SCL 后,人眼角膜基质中的鞘脂、磷脂酰肌醇 3-激酶蛋白激酶 B 和缺氧诱导因子-1 信号通路被激活。

结论

SCL 长期使用后,人眼角膜基质中与炎症相关的蛋白质组成分增加,可能是角膜基质损伤分子发病机制的重要因素。

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