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亚洲原发性开角型青光眼眼中房水蛋白质的失调。

Aqueous humour protein dysregulation in Asian eyes with primary open angle glaucoma.

机构信息

Department of Ophthalmology, Tan Tock Seng Hospital, National Healthcare Group Eye Institute, 11 Jalan Tan Tock Seng, 308433, Singapore.

Department of Ophthalmology, Tan Tock Seng Hospital, National Healthcare Group Eye Institute, 11 Jalan Tan Tock Seng, 308433, Singapore; Department of Ophthalmology, Woodlands Health, National Healthcare Group Eye Institute, Singapore; Department of Ophthalmology, Mayo Clinic, Jacksonville, USA.

出版信息

Exp Eye Res. 2024 Jun;243:109887. doi: 10.1016/j.exer.2024.109887. Epub 2024 Apr 10.

DOI:10.1016/j.exer.2024.109887
PMID:38609044
Abstract

The pathophysiology of Primary Open Angle Glaucoma (POAG) remains poorly understood. Through proteomic analysis of aqueous humour (AH) from POAG patients, we aim to identify changes in protein composition of these samples compared to control samples. High resolution mass spectrometry-based TMT6plex quantitative proteomics analysis is performed on AH samples collected from POAG patients, and compared against a control group of patients with cataracts. Data are available via ProteomeXchange with identifier PXD033153. 1589 proteins were quantified from the aqueous samples using Proteome Discoverer version 2.2 software. Among these proteins, 210 were identified as unique master proteins. The proteins which were up or down-regulated by ±3 fold-change were considered significant. Human neuroblastoma full-length cDNA clone CS0DD006YL02 was significantly upregulated in patients with severe POAG on >2 medications, while actin, cytoplasmic 1, V2-7 protein (fragment), immunoglobulin-like polypeptide 1 and phosphatidylethanolamine-binding protein 4 were only present in these patients with severe POAG on >2 medications. Beta-crystallin B1 and B2, Gamma-crystallin C, D and S were significantly downregulated in the severe POAG ≤2 glaucoma medications group. Beta-crystallin B2, Gamma-crystallin D and GCT-A9 light chain variable region (fragment) were significantly downregulated in the non-severe POAG group. Actin, cytoplasmic 1 was significantly upregulated in subjects with severe POAG who required more than 2 glaucoma medications. Crystallins (Beta-crystallin B1 and B2, Gamma-crystallin C, D and S) were significantly downregulated in subjects with severe POAG who required less than 2 glaucoma medications.

摘要

原发性开角型青光眼(POAG)的病理生理学仍知之甚少。通过对 POAG 患者房水(AH)的蛋白质组学分析,我们旨在确定与对照样品相比,这些样品中蛋白质组成的变化。对从 POAG 患者收集的 AH 样本进行基于高分辨率质谱的 TMT6plex 定量蛋白质组学分析,并与白内障对照组患者进行比较。数据可通过 ProteomeXchange 以标识符 PXD033153 获得。使用 Proteome Discoverer 版本 2.2 软件从水样中定量了 1589 种蛋白质。在这些蛋白质中,有 210 种被鉴定为独特的主蛋白质。认为 ±3 倍变化的上调或下调的蛋白质是显著的。在接受>2 种药物治疗的严重 POAG 患者中,人神经母细胞瘤全长 cDNA 克隆 CS0DD006YL02 显著上调,而肌动蛋白、细胞质 1、V2-7 蛋白(片段)、免疫球蛋白样多肽 1 和磷酸乙醇胺结合蛋白 4 仅存在于这些接受>2 种药物治疗的严重 POAG 患者中。在严重 POAG≤2 种青光眼药物组中,β-晶体蛋白 B1 和 B2、γ-晶体蛋白 C、D 和 S 显著下调。在非严重 POAG 组中,β-晶体蛋白 B2、γ-晶体蛋白 D 和 GCT-A9 轻链可变区(片段)显著下调。在需要超过 2 种青光眼药物的严重 POAG 患者中,肌动蛋白、细胞质 1 显著上调。在需要少于 2 种青光眼药物的严重 POAG 患者中,晶体蛋白(β-晶体蛋白 B1 和 B2、γ-晶体蛋白 C、D 和 S)显著下调。

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