Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
Ophthalmology Department of People's Hospital of Hotan District, Xinjiang, China.
J Cell Mol Med. 2021 Mar;25(6):3063-3079. doi: 10.1111/jcmm.16361. Epub 2021 Feb 17.
Primary open-angle glaucoma (POAG) is characterized by irreversible neurodegeneration accompanied by visual field defects and high intraocular pressure. Currently, an effective treatment is not available to prevent the progression of POAG, other than treatments to decrease the high intraocular pressure. We performed proteomic analysis of aqueous humour (AH) samples from patients with POAG combined with cataract and patients with cataract to obtain a better understanding of the pathogenesis of POAG and explore potential treatment targets for this condition. Samples were collected from 10 patients with POAG combined with cataract and 10 patients with cataract. Samples from each group were pooled. A high-resolution, label-free, liquid chromatography-tandem mass spectrometry-based quantitative proteomic analysis was performed. In total, 610 proteins were identified in human AH samples from the two groups. A total of 48 up-regulated proteins and 49 down-regulated proteins were identified in the POAG combined with cataract group compared with the control group. Gene Ontology (GO) analysis revealed key roles for these proteins in inflammation, immune responses, growth and development, cellular movement and vesicle-mediated transport in the biological process category. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated the down-regulated expression of glutathione S-transferase P (GSTP1) in the glutathione metabolism signalling pathway in the POAG combined with cataract group. Additionally, certain significantly differentially expressed proteins in the proteomic profile were verified by enzyme-linked immunosorbent assay (ELISA). GSTP1 levels were reduced in the human AH samples from the POAG combined with cataract group, based on the results of ELISA and proteomic profiling. Therefore, GSTP1, a redox-related marker, may be involved in the pathological process of POAG and may become a treatment target in the future.
原发性开角型青光眼（POAG）的特征是伴有视野缺损和高眼压的不可逆神经退行性变。目前，除了降低高眼压的治疗方法外，尚无有效的方法可以预防 POAG 的进展。我们对 POAG 合并白内障和单纯白内障患者的房水（AH）样本进行了蛋白质组学分析，以更好地了解 POAG 的发病机制，并探索该疾病的潜在治疗靶点。从 10 例 POAG 合并白内障和 10 例单纯白内障患者中采集样本。将每组样本混合。进行了基于高分辨率、无标记、液相色谱-串联质谱的定量蛋白质组学分析。在两组患者的 AH 样本中共鉴定出 610 种蛋白质。与对照组相比，POAG 合并白内障组有 48 种上调蛋白和 49 种下调蛋白。GO 分析显示，这些蛋白在炎症、免疫反应、生长发育、细胞运动和小泡介导的运输等生物学过程中起关键作用。京都基因与基因组百科全书（KEGG）分析表明，POAG 合并白内障组谷胱甘肽 S-转移酶 P（GSTP1）在谷胱甘肽代谢信号通路中的表达下调。此外，蛋白质组学分析中某些显著差异表达的蛋白通过酶联免疫吸附测定（ELISA）得到验证。ELISA 和蛋白质组学分析结果表明，POAG 合并白内障组患者的人 AH 样本中 GSTP1 水平降低。因此，GSTP1 作为一种与氧化还原相关的标志物，可能参与了 POAG 的病理过程，未来可能成为治疗靶点。
