School of Biological Sciences , Nanyang Technological University , Singapore 639798.
Renmin Hospital of Wuhan University , Wuhan , Hubei 430072 , PR China.
J Proteome Res. 2018 Jul 6;17(7):2499-2510. doi: 10.1021/acs.jproteome.8b00244. Epub 2018 Jun 26.
Primary open angle glaucoma (POAG) is a complex disease and a leading cause of irreversible blindness, and its underlying pathophysiology remains poorly understood. Proteomic characterization of the protein composition of aqueous humor (AH) may identify prognostic candidate proteins involved in pathogenesis and progression of the disease. To delineate the possible mechanisms that lead to POAG, this study adopted state-of-art mass spectrometric technique and analyzed AH of POAG and their respective controls. In total, more than 1000 proteins were identified with false discovery rate of less than 1%. Numerous proteins of complement cascade, immunoglobulin, neuronal and amyloidogenic proteins, which were part of processes like acute-phase and inflammatory response, humoral immune and acute inflammatory response, regulation of complement activation and protein processing were identified. Proteins of complement system underwent significant changes, which correlate to pathogenic events characterizing POAG, including altered complement cascade, astrocyte activation, neural degeneration, and apoptosis. Further, protein modification such as deamidation of complement subcomponent was noted, particularly in POAG. Proteomic analysis of AH allows a better understanding of the mechanism involved in the pathogenesis of POAG.
原发性开角型青光眼 (POAG) 是一种复杂的疾病，也是导致不可逆性失明的主要原因，其潜在的病理生理学仍知之甚少。对房水 (AH) 中蛋白质组成的蛋白质组学特征进行分析，可能会发现与疾病发病机制和进展相关的预后候选蛋白。为了阐明导致 POAG 的可能机制，本研究采用了最先进的质谱技术，分析了 POAG 患者和对照组的 AH。总共鉴定出了 1000 多种蛋白质，假发现率低于 1%。大量补体级联、免疫球蛋白、神经元和淀粉样蛋白相关的蛋白质被鉴定出来，这些蛋白质参与了急性期和炎症反应、体液免疫和急性炎症反应、补体激活和蛋白质加工的调节等过程。补体系统的蛋白质发生了显著变化，与 POAG 特征性的致病事件相关，包括补体级联的改变、星形胶质细胞的激活、神经变性和细胞凋亡。此外，还观察到蛋白质修饰，如补体亚成分的脱酰胺，特别是在 POAG 中。AH 的蛋白质组学分析可以更好地理解 POAG 发病机制中涉及的机制。
