Dataset Information

Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma.

ABSTRACT: Previous reports have shown possible association between altered protein levels in aqueous humor (AH) and normal-tension glaucoma (NTG), but the underlying pathogenetic mechanism as well as specific molecular biomarkers for NTG remains still elusive. Here, we aimed to identify novel biomarkers for advanced NTG by analyzing the proteome of patient-derived AH and their correlation with various functional and structural parameters from the visual field test (VF), optical coherence tomography (OCT), and OCT angiography (OCTA). We determined differentially expressed proteins (DEPs) of the AH of patients with advanced NTG (n = 20) using label-free quantitative (LFQ) proteomics with pooled samples and data-independent acquisition (DIA) analysis with individual samples, and the roles of AH DEPs in biological pathways were evaluated using bioinformatics. We identified 603 proteins in the AH of patients with advanced NTG, and 61 of them were selected as DEPs via global proteome LFQ profiling. Individual DIA analyses identified a total of 12 DEPs as biomarker candidates, seven of which were upregulated, and five were downregulated. Gene ontology enrichment analysis revealed that those DEPs were mainly involved in the immune response. Moreover, IGFBP2, ENO1, C7, B2M, AMBP, DSP, and DCD showed a significant correlation with the mean deviation of VF and with peripapillary and macular parameters from OCT and OCTA. The present study provides possible molecular biomarkers for the diagnosis of advanced NTG.

SUBMITTER: Lee SH

PROVIDER: S-EPMC8786875 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma.

Lee Si Hyung SH Jung Jae Hun JH Park Tae Kwann TK Moon Chae-Eun CE Han Kyusun K Lee Jinhyoung J Lee Hyung Keun HK Ji Yong Woo YW Kim Chan Yun CY

Scientific reports 20220124 1

Previous reports have shown possible association between altered protein levels in aqueous humor (AH) and normal-tension glaucoma (NTG), but the underlying pathogenetic mechanism as well as specific molecular biomarkers for NTG remains still elusive. Here, we aimed to identify novel biomarkers for advanced NTG by analyzing the proteome of patient-derived AH and their correlation with various functional and structural parameters from the visual field test (VF), optical coherence tomography (OCT), ...[more]

PMID: 35075201

Similar Datasets

Project description:Fuchs endothelial corneal dystrophy (FECD) is a progressive disorder characterized by corneal endothelial decompensation leading to corneal edema, clouding, and vision impairment. Despite improved understanding over the last century since its first description, the exact mechanism(s) behind the pathogenesis of FECD remain unknown, and surgical correction is the only effective treatment available. Previous studies have suggested a role for changes in aqueous humor (AH) composition in FECD pathogenesis, so to explore this possibility, we probed the AH proteome for alterations correlating with end-stage corneal disease. Following albumin depletion we performed label-free quantitative tandem mass spectrometry on proteins isolated from patients with and without FECD who were scheduled to undergo routine cataract extraction. We identified 64 proteins, most of which were identified in previous AH proteomic studies of patients with cataracts, in the albumin-depleted fraction. The levels of five of these were significantly lower (afamin, complement C3, histidine-rich glycoprotein, immunoglobulin heavy [IgH], and protein family with sequence similarity 3, member C [FAM3C]), while the levels of one (suprabasin) was significantly higher in patients with FECD compared to controls (p≤0.01). We also identified 34 proteins in the albumin-bound fraction, four of which were significantly elevated in patients with FECD including a hemoglobin fragment, immunoglobulin kappa (IgK), immunoglobulin lambda (IgL), and uncharacterized protein albumin (ALB), (p≤0.01). Although it has been reported that females have a greater extent of disease than males, we were unable to detect any significant differences in protein levels due to gender. Because FECD is a progressive disorder, regression analyses were performed to determine any significant correlations with age, and of interest retinol-binding protein 3 was significantly correlated with age in patients with FECD (p≤0.01), whereas no proteins in the control group correlated with age. This is the first report indicating alterations in the AH proteome with FECD, and taken together this study suggests several novel hypotheses regarding AH proteins role in FECD pathogenesis.

Project description:Analysis of the proteins of the aqueous humor can help to elucidate the complex pathogenesis of primary open angle glaucoma. Thanks to advances in liquid chromatography tandem mass spectrometry (LC-MS/MS) it is now possible to identify hundreds of proteins in individual aqueous humor samples without the need to pool samples. We performed a systematic literature search to find publications that performed LC-MS/MS on aqueous humor samples of glaucoma patients and of non-glaucomatous controls. Of the seven publications that we found, we obtained the raw data of three publications. These three studies used glaucoma patients that were clinically similar (i.e. undergoing glaucoma filtration surgery) which prompted us to reanalyse and combine their data. Raw data of each study were analysed separately with the latest version of MaxQuant (version v1.6.11.0). Outcome files were exported to Microsoft Excel. Samples belonging to the same patient were averaged to obtain peptide expression values per individual. We compared the overlap of identified proteins using the VLOOKUP function of Excel and a publicly available Venn diagram software. For the peptide sequences that can belong to multiple proteins (usually of the same protein family), we initially included all possibly identified proteins. This ensured that we would not miss a potential overlap between the studies due to differences in identified peptide counts. Next, of those peptides of which we compared multiple proteins, only one unique protein was included in our analysis i.e. either the protein overlapping between studies or in case of no overlap, the protein that had the highest identified peptide count. This yielded 639 unique proteins detected in aqueous humor of either glaucoma patients or non-glaucomatous controls. In our manuscript entitled "The aqueous humor proteome of primary open angle glaucoma: An extensive review" [1], we further analysed this dataset. The dataset was exported to Perseus (version 1.6.5.0). We removed contaminants and filtered for proteins detected with high confidence, i.e. in more than 70% of the samples of at least one study. This yielded 248 proteins of which we compared the expression in glaucoma patients against control patients. Gene ontology enrichment analysis and pathway analysis was used to interpret the results. The unfiltered dataset reported in this data article and the approach reported here to reanalyse and combine raw data of different studies can be applied by other glaucoma researchers to gain more insight in the pathogenesis of glaucoma.

Project description:ObjectiveTo characterize the 24-h habitual-position intraocular pressure (IOP) patterns of optic disc phenotypes (ODPs) in untreated normal-tension glaucoma (NTG) and the relationships between nocturnal IOP elevation and various clinical factors.DesignProspective, cross-sectional, observational study.MethodsEighty-two NTG patients with focal ischemic (FI) ODP and 82 age- and disease severity-matched NTG patients with myopic glaucomatous (MG) ODP were recruited prospectively over 3 years. The IOP was recorded 11 times over a 24-hour (h) period by a single ophthalmologist using a hand-held tonometer (TonoPen®XL). A cosinor model was used to describe the 24-h IOP rhythm. Associations between nocturnal IOP elevation and both ocular and demographic variables were evaluated using the generalized estimating equation (GEE).ResultsMean habitual-position IOP was significantly higher during nighttime than daytime in the FI group (16.44 vs. 14.23 mmHg, P < 0.001), but not in the MG group (15.91 vs. 15.70 mmHg, P = 0.82). The FI group also exhibited a significantly higher peak IOP during sleeping hours (P = 0.01) and lower trough IOP during the 24-h period than the MG group (P < 0.01). The MG group showed a significantly higher peak IOP during waking hours than the FI group (P < 0.01). Therefore, 24-h IOP fluctuation range was significantly higher in the FI group than the MG group (P = 0.013). In the FI group, peak habitual-position IOP and the highest frequency of IOP peaks occurred during sleeping hours (12 AM-6 AM). By contrast, IOP peaks in the MG group occurred during morning hours (8 AM-12 PM). The FI group showed an overall nocturnal acrophase in habitual-position IOP, with 45 patients (54.9%) having a nocturnal acrophase; 10 (12.2%), a diurnal acrophase; and 27 (32.9%), no evident acrophase. By contrast, the MG group showed no evident peak in habitual-position IOP, with 9 patients (10.9%) having a nocturnal acrophase; 43 (52.4%), a diurnal acrophase; and 30 (36.6%), no evident acrophase. In multivariate modeling using the GEE, ODP (P < 0.001) and spherical equivalent (SE, P = 0.001) were independently associated with nocturnal IOP elevation.ConclusionsBased on 24-h habitual-position IOP data, FI is associated with significant nocturnal IOP elevation, while no such nocturnal IOP elevation is observed in MG ODP. In untreated NTG, there are also significant differences in the 24-h IOP pattern between FI and MG ODPs.

Dataset Information

Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma.

Publications

Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets