Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Ophthalmology Department of People's Hospital of Hotan District, Xinjiang, China.
Exp Eye Res. 2024 Jun;243:109903. doi: 10.1016/j.exer.2024.109903. Epub 2024 Apr 18.
Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.
假性剥脱综合征（PEX）的特征是眼内纤维状假性剥脱物（PEXM）的沉积，与该综合征相关的继发性青光眼具有更快和更严重的临床病程。PEX 和假性剥脱性青光眼（PEXG）的发病率表现出种族聚集性；然而，在亚洲人群中进行的与 PEX 和 PEXG 相关的蛋白质组学研究较少。因此，我们旨在对维吾尔族白内障患者、PEX 合并白内障患者和 PEXG 合并白内障患者的房水（AH）进行蛋白质组学分析，以更好地了解疾病的分子机制并确定其潜在的生物标志物。为此，我们在白内障超声乳化术中收集了白内障患者（n=10，对照组）、PEX 合并白内障患者（n=10，PEX 组）和 PEXG 合并白内障患者（n=10，PEXG 组）的 AH。采用无标记定量蛋白质组学技术结合生物信息学方法，鉴定和分析 PEX 和 PEXG 组 AH 中的差异表达蛋白（DEPs）。然后，通过酶联免疫吸附试验（ELISA）收集独立的 AH 样本（n=12，每组）来验证 DEPs。与对照组相比，PEX 组有 25 个 DEPs，PEXG 组有 44 个 DEPs。随后，我们在 PEX 和 PEXG 两组中发现了三个新鉴定的蛋白，其中 FRAS1 相关细胞外基质蛋白 2（FREM2）和破骨细胞相关受体（OSCAR）下调，而凝血因子 IX（F9）上调。生物信息学分析表明，细胞外基质相互作用、异常血液来源蛋白和溶酶体主要参与 PEX 和 PEXG 过程，PPI 网络进一步表明 F9 可能是 PEX 和 PEXG 的潜在生物标志物。总之，本研究为了解 PEX 和 PEXG 中 AH 的蛋白质组学提供了新信息。
