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Proteomics and phosphoproteomics analysis of the vitreous in idiopathic epiretinal membrane patients

ABSTRACT: Purpose: The purpose of present study is to characterize the Idiopathic epiretinal membrane (iERM) through phosphoproteomics to facilitate its diagnosis and treatment. Experimental design: The vitreous of 25 patients with iERM and 15 patients with idiopathic macular hole were analyzed by proteomic and phosphoproteomic analysis based on tandem mass tag. PRM was used to verify differential proteins. Results: Proteomic analysis identified a total of 878 proteins, including 50 differential proteins. Phosphoproteomic analysis identified a total of 401 phosphorylation sites on 213 proteins, including 27 differential phosphorylation sites on 24 proteins. Twenty six proteins of these differential proteins and phosphorylated proteins may be closely related to fibrosis in iERM. MAPKAPK3 and MAPKAPK5 are predicted as the major kinases in vitreous of iERM. Conclusion and clinical relevance: Our results screened candidate proteins for the treatment of fibrosis in iERM, among which tenascin-C, galectin-3-binding protein, glucose-6-phosphate isomerase, neuroserpin, collagen alpha-1(XI) chain and collagen alpha-1(II) chain are expected to become potential biomarkers or therapeutic targets for iERM. In addition, this article expand the data of vitreous phosphoproteome, and provide a reference resource and new enlightenment for studying the pathogenic mechanisms of retinal diseases.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Eye

SUBMITTER: Chao Sun

LAB HEAD: chao sun

PROVIDER: PXD030278 | Pride | 2023-12-04

REPOSITORIES: Pride

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Proteomics and phosphoproteomics analysis of vitreous in idiopathic epiretinal membrane patients.

Sun Chao C Zou Huan H Yang Zhouquan Z Yang Mei M Chen Xiaofan X Huang Yanming Y Fan Wei W Yuan Rongdi R

Proteomics. Clinical applications 20220511 5

<h4>Purpose</h4>The purpose of the present study was to characterize the idiopathic epiretinal membrane (iERM) through proteomics and phosphoproteomics analysis to facilitate the diagnosis and treatment of iERM.<h4>Experimental design</h4>The vitreous of 25 patients with an iERM and 15 patients with an idiopathic macular hole were analyzed by proteomic and phosphoproteomic analysis based on tandem mass tag. PRM was used to verify the differential proteins.<h4>Results</h4>Proteomic analysis ident ...[more]

PMID: 35510950

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Project description:Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are leading causes of visual impairment and blindness in people aged 50 years or older in middle-income and industrialized countries. Anti-VEGF therapies have improved the management of neovascular AMD (nAMD) and proliferative DR (PDR), no treatment options exist for the highly prevalent dry form of AMD. To unravel the biological processes underlying these pathologies and to find new potential biomarkers, a label-free quantitative (LFQ) method was applied to analyze the vitreous proteome in PDR (n=4), AMD (n=4) compared to idiopathic epiretinal membranes (ERM) (n=4). Post-hoc tests revealed 96 proteins capable of differentiating among the different groups, whereas 118 proteins were found differentially regulated in PDR compared to ERM and 95 proteins in PDR compared to dry AMD. The pathway analysis indicates that mediators of complement and coagulation cascades and acute phase responses are enriched in PDR vitreous, whilst proteins highly correlated to the extracellular matrix (ECM) organization, platelet degranulation, lysosomal degradation, cell adhesion, and central nervous system development were found underexpressed. According to these results, 35 proteins were selected and validated by MRM (multiple reaction monitoring) in a larger cohort of patients with ERM (n=21), DR/PDR (n=20), AMD (n=11), and retinal detachment (n=13). Of these, 26 proteins were validated and were capable of differentiating between vitreoretinal diseases under study. Based on Partial least squares discriminant and multivariate exploratory receiver operating characteristic (ROC) analyses, a panel of 15 discriminatory biomarkers was defined, which includes complement and coagulation components (CO2 and prothrombin), acute-phase mediators (alpha-1-antichymotrypsin), adhesion molecules (e.g., myocilin, galectin-3-binding protein), ECM components (opticin), and neurodegeneration biomarkers (beta-amyloid, amyloid-like protein 2).

Dataset Information

Proteomics and phosphoproteomics analysis of the vitreous in idiopathic epiretinal membrane patients

Publications

Proteomics and phosphoproteomics analysis of vitreous in idiopathic epiretinal membrane patients.

Similar Datasets

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