Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
J Proteomics. 2023 Aug 15;285:104949. doi: 10.1016/j.jprot.2023.104949. Epub 2023 Jun 17.
Myopia is one of the most common causes of visual impairment worldwide. To identify proteins related to myopiagenesis, data-independent acquisition proteomic analysis was performed using corneal lenticules of myopic patients who underwent small incision lenticule extraction surgery. A total of 19 lenticules from 19 age and sex-matched patients were analyzed, 10 in high refractive error (HR, spherical equivalent over -6.00 D) group and 9 in low refractive error (LR, spherical equivalent between -3.00 and - 1.00 D) group. Differentially expressed proteins (DEPs) were identified by comparing the corneal proteome between the two groups. Functional analyses were performed to explore the biological pathways and interactions of the DEPs. 107 DEPs (67 upregulated and 40 downregulated in HR group, compared to LR) were identified from 2138 quantified proteins. Functional analyses indicated that upregulated proteins were primarily involved in the complement pathways and extracellular matrix (ECM) remodeling, while downregulated proteins were involved in mitochondrial energy metabolism. Western blot analysis confirmed increased complement C3a and apolipoprotein E in HR samples, further supporting the proteomics data. In conclusion, this proteomic study reveals that proteins associated with the complement system, ECM remodeling, and mitochondrial energy metabolism might be key effectors in myopiagenesis. SIGNIFICANCE: Myopia has become one of the most prevalent causes of visual impairment, especially in Asia. The underlying mechanism of myopia development is still up for debate. This study compares the proteomic profiles of high and low myopic corneas, identifying differentially expressed proteins associated with the complement system, ECM remodeling, and mitochondrial energy metabolism. The findings of this study could provide novel insights into the pathogenesis of myopia. The complement system and mitochondrial energy metabolism may provide potential therapeutic targets in the treatment and prevention of myopia.
近视是全球最常见的视力损害原因之一。为了鉴定与近视形成相关的蛋白，我们对接受小切口微透镜切除术的近视患者的角膜透镜进行了非依赖性采集蛋白质组学分析。分析了 19 名年龄和性别匹配的患者的 19 个透镜，其中 10 个来自高度近视（等效球镜值超过-6.00D）组，9 个来自低度近视（等效球镜值在-3.00 至-1.00D 之间）组。通过比较两组之间的角膜蛋白质组，鉴定差异表达蛋白（DEPs）。对 DEPs 进行功能分析，以探索其生物学途径和相互作用。从 2138 个定量蛋白质中鉴定出 107 个 DEPs（HR 组中 67 个上调，40 个下调，与 LR 组相比）。功能分析表明，上调的蛋白主要参与补体途径和细胞外基质（ECM）重塑，而下调的蛋白则参与线粒体能量代谢。Western blot 分析证实 HR 样本中补体 C3a 和载脂蛋白 E 增加，进一步支持蛋白质组学数据。总之，这项蛋白质组学研究表明，与补体系统、ECM 重塑和线粒体能量代谢相关的蛋白可能是近视形成的关键效应物。意义：近视已成为视力损害的最常见原因之一，尤其是在亚洲。近视发展的潜在机制仍存在争议。本研究比较了高低近视眼角膜的蛋白质组特征，鉴定出与补体系统、ECM 重塑和线粒体能量代谢相关的差异表达蛋白。本研究的发现可为近视发病机制提供新的见解。补体系统和线粒体能量代谢可能为近视的治疗和预防提供潜在的治疗靶点。
