Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Shanghai, China; Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China; Fudan University Shanghai Medical College, Shanghai 200032, China.
Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia (Fudan University), Shanghai, China; Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.
Exp Eye Res. 2024 Jan;238:109726. doi: 10.1016/j.exer.2023.109726. Epub 2023 Nov 17.
This study aimed to investigate the underlying pathophysiology of high myopia by analyzing the proteome of human corneal stromal lenticule samples obtained through small incision lenticule extraction (SMILE). A total of thirty-two patients who underwent SMILE were included in the study. Label-free quantitative proteomic analysis was performed on corneal stromal lenticule samples, equally representing high myopia (n = 10) and low myopia (n = 10) groups. The identified and profiled lenticule proteomes were analyzed using in silico tools to explore biological characteristics of differentially expressed proteins (DEPs). Additionally, LASSO regression and random forest model were employed to identify key proteins associated with the pathophysiology of high myopia. The DEPs were found to be closely linked to immune activation, extracellular matrix, and cell adhesion-related pathways according to gene ontology analysis. Specifically, decreased expression of COL1A1 and increased expression of CDH11 were associated with the pathogenesis of high myopia and validated by western blotting (n = 6) and quantitative real time polymerase chain reaction (n = 6). Overall, this study provides evidence that COL1A1 and CDH11 may contribute to the pathophysiology of high myopia based on comparative proteomic profiling of human corneal stromal lenticules obtained through SMILE.
本研究旨在通过分析通过小切口微透镜提取术（SMILE）获得的人眼角膜基质透镜样本的蛋白质组，来研究高度近视的潜在病理生理学。共有 32 名接受 SMILE 的患者纳入本研究。对角膜基质透镜样本进行无标记定量蛋白质组学分析，分别代表高度近视（n=10）和低度近视（n=10）组。使用计算工具分析鉴定和描绘的透镜蛋白质组，以探索差异表达蛋白（DEP）的生物学特征。此外，还使用 LASSO 回归和随机森林模型来识别与高度近视病理生理学相关的关键蛋白。根据基因本体分析，差异表达蛋白与免疫激活、细胞外基质和细胞黏附相关途径密切相关。具体而言，COL1A1 的表达降低和 CDH11 的表达增加与高度近视的发病机制相关，并通过 Western 印迹（n=6）和定量实时聚合酶链反应（n=6）验证。总的来说，这项研究基于 SMILE 获得的人眼角膜基质透镜的比较蛋白质组学分析，为 COL1A1 和 CDH11 可能导致高度近视的病理生理学提供了证据。
