Abstract

BACKGROUND: Glucocorticoids (GCs)-induced glaucoma is a common adverse effect of prolonged GCs use. To better understand the effects of GCs on aqueous humor (AH) outflow, we analyzed the dataset GSE37474 using bioinformatics analysis to identify gene changes and pathways in the anterior segment of the human eye induced by dexamethasone (DEX).

MATERIAL AND METHODS: The GSE37474 dataset downloaded from the Gene Expression Omnibus (GEO) database was examined in this study. GEO2R was utilized to analyze data and identify differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were constructed using the DAVID database followed by construction of a protein–protein interaction (PPI) network performed using Cytoscape software. Finally, modules and hub genes were screened out using MCODE and cytoHubba plugin, respectively.

RESULTS: A set of 252 DEGs were screened. Among the DEGs, 143 genes were upregulated and 109 were downregulated. GO analysis indicated that some of the DEGs participated in extracellular matrix (ECM) organization and cholesterol homeostasis. Additionally, KEGG pathways were predominantly enriched in tyrosine metabolism and ECM-receptor interaction. From the PPI network, 2 modules were identified, and 10 hub genes were screened out, including CCL2, FOS, IGF1, PTGS2, CCL5, EDN1, IL11, F3, PMCH, and BDKRB1. The 2 module genes primarily participate in the TNF signaling pathway, cytokine-cytokine receptor interaction, and the Jak-STAT signaling pathway.

CONCLUSIONS: The present study identified some significant DEGs, hub genes, pathways, and modules in the human anterior segment induced by DEX. These results demonstrate that DEX changes the expression of certain genes and pathways to resist aqueous humor outflow, which could be new targets for developing novel and more effective approaches of diagnosis and therapy for GCs-induced glaucoma.

Keywords: Dexamethasone, Gene Expression Profiling, Glaucoma, Aqueous Humor, Computational Biology, Databases, Genetic, Eye, gene ontology, Glucocorticoids, Protein Interaction Mapping, Protein Interaction Maps, Software, transcriptome