Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus

Abstract Glaucoma is the primary factor underlying irreversible blindness. Recent studies suggest that the risk of glaucoma significantly increases in patients with systemic lupus erythematosus (SLE); however, the mechanism underlying this association remains unclear. Therefore, this study aimed to...

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Main Authors: Yixian Liu, Mengling You, Zhou Zeng, Jing Wang, Rong Rong, Xiaobo Xia
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:iMetaOmics
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Online Access:https://doi.org/10.1002/imo2.27
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author Yixian Liu
Mengling You
Zhou Zeng
Jing Wang
Rong Rong
Xiaobo Xia
author_facet Yixian Liu
Mengling You
Zhou Zeng
Jing Wang
Rong Rong
Xiaobo Xia
author_sort Yixian Liu
collection DOAJ
description Abstract Glaucoma is the primary factor underlying irreversible blindness. Recent studies suggest that the risk of glaucoma significantly increases in patients with systemic lupus erythematosus (SLE); however, the mechanism underlying this association remains unclear. Therefore, this study aimed to identify novel common biomarkers and potential therapeutic drugs for SLE and glaucoma. GSE27276, GSE50772, and GSE148371 datasets were sourced from the gene expression omnibus (GEO) database. An integrated analysis of the datasets for both diseases identified biomarkers and thoroughly examined their biological roles and molecular mechanisms using differential expression analysis (DEA), weighted gene co‐expression network analysis (WGCNA), gene enrichment analysis, machine learning, microRNA (miRNA) and transcription factor analyses, immune infiltration analyses, and single‐cell transcriptome analysis. Concurrently, molecular docking was used to forecast potential drugs targeting these biomarkers. Finally, reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR) was performed in human trabecular meshwork stem cells to validate the five identified biomarkers. The 10 key genes identified through DEA and WGCNA were predominantly involved in immune, inflammatory, and autophagy pathways. Additionally, machine learning identified five biomarkers, and we established associated transcription factors and miRNA regulatory networks. Immune infiltration analysis indicated an elevated presence of immune cells, including macrophages, T cells, and B cells, in both conditions. Furthermore, the DSigDB database yielded 10 potential therapeutic agents, three of which showed strong binding potential to the biomarkers via molecular docking. The RT‐qPCR results confirmed the trend in gene expression. This study uncovered a new link between SLE and primary open‐angle glaucoma, identifying biomarkers and mechanisms of immunopathogenesis for future research and treatment strategies.
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spelling doaj-art-f2a7980ab2294458ae79c38bac673fa32025-01-31T16:15:24ZengWileyiMetaOmics2996-95062996-95142024-12-0112n/an/a10.1002/imo2.27Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosusYixian Liu0Mengling You1Zhou Zeng2Jing Wang3Rong Rong4Xiaobo Xia5Eye Center of Xiangya Hospital Central South University Changsha ChinaEye Center of Xiangya Hospital Central South University Changsha ChinaEye Center of Xiangya Hospital Central South University Changsha ChinaEye Center of Xiangya Hospital Central South University Changsha ChinaEye Center of Xiangya Hospital Central South University Changsha ChinaEye Center of Xiangya Hospital Central South University Changsha ChinaAbstract Glaucoma is the primary factor underlying irreversible blindness. Recent studies suggest that the risk of glaucoma significantly increases in patients with systemic lupus erythematosus (SLE); however, the mechanism underlying this association remains unclear. Therefore, this study aimed to identify novel common biomarkers and potential therapeutic drugs for SLE and glaucoma. GSE27276, GSE50772, and GSE148371 datasets were sourced from the gene expression omnibus (GEO) database. An integrated analysis of the datasets for both diseases identified biomarkers and thoroughly examined their biological roles and molecular mechanisms using differential expression analysis (DEA), weighted gene co‐expression network analysis (WGCNA), gene enrichment analysis, machine learning, microRNA (miRNA) and transcription factor analyses, immune infiltration analyses, and single‐cell transcriptome analysis. Concurrently, molecular docking was used to forecast potential drugs targeting these biomarkers. Finally, reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR) was performed in human trabecular meshwork stem cells to validate the five identified biomarkers. The 10 key genes identified through DEA and WGCNA were predominantly involved in immune, inflammatory, and autophagy pathways. Additionally, machine learning identified five biomarkers, and we established associated transcription factors and miRNA regulatory networks. Immune infiltration analysis indicated an elevated presence of immune cells, including macrophages, T cells, and B cells, in both conditions. Furthermore, the DSigDB database yielded 10 potential therapeutic agents, three of which showed strong binding potential to the biomarkers via molecular docking. The RT‐qPCR results confirmed the trend in gene expression. This study uncovered a new link between SLE and primary open‐angle glaucoma, identifying biomarkers and mechanisms of immunopathogenesis for future research and treatment strategies.https://doi.org/10.1002/imo2.27immune infiltrationmolecular dockingprimary open‐angle glaucomasingle cell transcriptomesystemic lupus erythematosustargeted drugs
spellingShingle Yixian Liu
Mengling You
Zhou Zeng
Jing Wang
Rong Rong
Xiaobo Xia
Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus
iMetaOmics
immune infiltration
molecular docking
primary open‐angle glaucoma
single cell transcriptome
systemic lupus erythematosus
targeted drugs
title Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus
title_full Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus
title_fullStr Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus
title_full_unstemmed Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus
title_short Novel insights into immunopathogenesis and crucial biomarkers between primary open‐angle glaucoma and systemic lupus erythematosus
title_sort novel insights into immunopathogenesis and crucial biomarkers between primary open angle glaucoma and systemic lupus erythematosus
topic immune infiltration
molecular docking
primary open‐angle glaucoma
single cell transcriptome
systemic lupus erythematosus
targeted drugs
url https://doi.org/10.1002/imo2.27
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