Oxidative stress (OS) plays an important role in trabecular meshwork (TM) dysfunction in glaucoma, but its molecular mechanism remains unclear. We integrated the GSE27276 dataset and OS-related gene sets from GeneCards to screen 61 differentially expressed OS-related genes (DEOSGs). Functional enrichment analysis revealed that these genes are primarily involved in inflammatory and OS-related signaling pathways, including IL-17, TNF, and NF-κB. A protein-protein interaction (PPI) network constructed via the STRING database identified seven hub genes (CCL3, CXCL1, NFKBIA, VCAM1, LCN2, TNFRSF1A, and HP). Validation using the GSE124114, GSE37474, and GSE65240 datasets showed that the expression of CXCL1 and VCAM1 was downregulated, while NFKBIA was upregulated. Additionally, all three genes exhibited an area under the curve (AUC) greater than 0.7. Immune infiltration analysis demonstrated significant associations between these genes and immune cells, particularly regulatory T cells and neutrophils. Regulatory network analysis suggested that transcription factors (RELA, NFKB1) and microRNAs (hsa-miR-34a-5p) may modulate these core genes. Drug-gene interaction studies identified 35 potential therapeutic agents, including Infliximab and Vitamin B6. This study systematically elucidates the molecular mechanisms of OS in glaucoma, proposing that the identified core genes and their regulatory networks not only serve as novel biomarkers for diagnosis but also provide a theoretical foundation for developing targeted therapeutic strategies.
Xu et al. (Mon,) studied this question.