Dataset Information

Comprehensive Proteomic Profiling of Vitreous Humor in Ocular Sarcoidosis Compared with Other Vitreoretinal Diseases.

ABSTRACT: Ocular sarcoidosis is an inflammatory disease that manifests as uveitis, and is often difficult to distinguish from other forms of uveitis based on nonspecific findings alone. Comprehensive proteomic analyses of vitreous humor using LC-MS/MS were performed in each patient with ocular sarcoidosis, vitreoretinal lymphoma (VRL), and controls with epiretinal membrane or macular hole. Differential expression proteins (DEPs) were identified by comparing with VRL and controls, and functional pathway analysis was performed. The candidate biomarker proteins for ocular sarcoidosis were validated using enzyme-linked immunosorbent assay. A total of 1590 proteins were identified in all samples. Of these, 290 and 174 DEPs were detected in vitreous of ocular sarcoidosis compared with controls and VRL, respectively. Enrichment pathway analysis revealed that pathways related to the immune system were most upregulated. Validation of two candidate biomarkers for ocular sarcoidosis, neutrophil gelatinase-associated lipocalin (NGAL) and junctional adhesion molecules B (JAMB), confirmed upregulated NGAL and JAMB protein expressions in ocular sarcoidosis compared to controls and VRL. The results of this study revealed that altered vitreous protein expression levels may discriminate ocular sarcoidosis from other uveitis diseases. Vitreous NGAL and JAMB are potential biomarkers and may serve as an auxiliary tool for the diagnosis of ocular sarcoidosis.

SUBMITTER: Komatsu H

PROVIDER: S-EPMC9267904 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Comprehensive Proteomic Profiling of Vitreous Humor in Ocular Sarcoidosis Compared with Other Vitreoretinal Diseases.

Komatsu Hiroyuki H Usui Yoshihiko Y Tsubota Kinya K Fujii Risa R Yamaguchi Takefumi T Maruyama Kazuichi K Wakita Ryo R Asakage Masaki M Shimizu Hiroyuki H Yamakawa Naoyuki N Nezu Naoya N Ueda Koji K Goto Hiroshi H

Journal of clinical medicine 20220622 13

Ocular sarcoidosis is an inflammatory disease that manifests as uveitis, and is often difficult to distinguish from other forms of uveitis based on nonspecific findings alone. Comprehensive proteomic analyses of vitreous humor using LC-MS/MS were performed in each patient with ocular sarcoidosis, vitreoretinal lymphoma (VRL), and controls with epiretinal membrane or macular hole. Differential expression proteins (DEPs) were identified by comparing with VRL and controls, and functional pathway an ...[more]

PMID: 35806888

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Project description:IntroductionDiabetic 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.MethodsTo 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).Results and discussionPost-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. Pathway analysis indicates that mediators of complement, 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 monitored 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 could differentiate between these vitreoretinal diseases. 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 (complement C2 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).

Project description:MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by post-transcriptional inhibition of mRNA translation. Dysregulation of miRNAs, including circulating miRNAs, has been reported to play an important role in the development of various diseases, including fibrotic diseases. Aberrant expression of miRNAs in the vitreous humor of vitreoretinal diseased eyes has been reported. However, the expression pattern of miRNAs present in the vitreous humor of proliferative vitreoretinal disease (PVD) patients, including proliferative diabetic retinopathy (PDR), and proliferative vitreoretinopathy (PVR), remains unknown. To investigate the factors important for the development of PVD, we characterized the miRNAs present in the vitreous humor of PVD patients and analyzed the expression profiles of 377 miRNAs using quantitative polymerase chain reaction-based miRNA arrays. The expression of a specific subset of miRNAs, previously reported to be associated with the development of angiogenesis and fibrosis, was significantly altered in the vitreous of PVD patients. Among these miRNAs, we identified miR-21 as a candidate fibrotic miRNA with an important role in the pathogenesis of PVD. Increased miR-21 levels in the vitreous were associated with retinal fibrosis, including PVR and PDR. Because epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPECs) plays a critical role in retinal fibrosis, the expression of miR-21 in human RPECs was determined. Its expression in RPECs was induced by transforming growth factor-β, a key growth factor involved in fibrogenesis, and was enhanced by high glucose culture conditions, suggesting that miR-21 expression positively correlates with disease progression. Gain- and loss-of-function studies revealed that miR-21 promoted cell proliferation and migration of ARPE-19 cells without affecting EMT-related gene expression. Together, our studies have identified miR-21 as a potential disease-modifying miRNA in the vitreous humor that is involved in the development of retinal fibrosis and may be a novel marker of PVD.

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

Comprehensive Proteomic Profiling of Vitreous Humor in Ocular Sarcoidosis Compared with Other Vitreoretinal Diseases.

Publications

Comprehensive Proteomic Profiling of Vitreous Humor in Ocular Sarcoidosis Compared with Other Vitreoretinal Diseases.

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