Stage-dependent proteomic alterations in aqueous humor of diabetic retinopathy patients based on data-independent acquisition and parallel reaction monitoring

作者：Yeanqi Jin, Junbin Liu, Xueli Zhang, Liang Zhang, Ying Cui, Xiaoyang Luo, Haoxian Zhu, Zhifan Chen, Mengya Liu, Xi‐Yu Wu, Xinyu Chen, Shuoxin Liao, Guanrong Wu, Xiang Fang, Qianli Meng · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06452-z · 被引用次数：9 · 研究领域：Retinal Diseases and Treatments、Retinal Imaging and Analysis、Retinal and Optic Conditions

BACKGROUND: Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), represents the predominant cause of preventable vision loss in working-age populations globally. While the pathophysiological mechanisms underlying DR progression remain incompletely understood, our study employs comprehensive proteomic profiling of aqueous humor (AH) to identify stage-specific biomarkers and therapeutic targets in type 2 diabetes mellitus (T2DM) patients across DR progression. METHODS: Utilizing data-independent acquisition (DIA) mass spectrometry, we quantified AH proteomes in a discovery cohort comprising 24 subjects: 18 T2DM patients stratified by DR severity [6 non-DR, 6 non-proliferative DR (NPDR), 6 proliferative DR (PDR)] and 6 cataract controls without diabetes (non-DM). Validation cohort analysis (including 10 AH samples in each group) was performed using parallel reaction monitoring (PRM) strategy for verification of target proteins. Comprehensive bioinformatics analyses included gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network construction, receiver operating characteristic (ROC) curve analysis, and ConnectivityMap (Cmap)-based drug prediction. RESULTS: Proteomic profiling identified 739 quantifiable AH proteins (62% extracellular) with clear separation among the four clinical stages in the discovery coho...