AIM:To profile gene expression changes induced by dexamethasone in human trabecular meshwork using bioinformatics analysis, and to elucidate the possible mechanisms involved in the pathogenesis of glucocorticoid-induced glaucoma(GIG).

METHODS:The gene expression dataset GSE37474 was obtained from the Gene Expression Omnibus(GEO). GEO2R was utilized to identify differentially expressed genes(DEGs)in trabecular meshwork between the dexamethasone group and the control group. Gene Ontology(GO)function annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were constructed using the DAVID database. STRING database and Cytoscape software were used to construct protein-protein interaction(PPI). The hub genes were screened by CytoHubba plug-in. Finally, the mRNA expression of key hub genes was verified by RT-PCR.

RESULTS:Compared to normal trabecular meshwork, dexamethasone-treated trabecular meshwork had a total of 252 DEGs, with 141 genes up-regulated and 111 genes down-regulated. GO function annotation showed that DEGs were mostly located in the extracellular matrix, where they engaged in the biological processes of positive regulation of inflammation and extracellular matrix remodeling. KEGG pathway enrichment showed that DEGs were largely involved in vascular smooth muscle contraction, arachidonic acid metabolism, ether lipid metabolism and choline metabolism. The PPI network yielded seven hub genes, three of which were up-regulated(EDN1, FOS, and LPL)and four of which were down-regulated(CCL2, IGF1, PTGS2, CCL5). In RT-PCR, the mRNA expression levels of the seven hub genes matched those in the gene expression profile.

CONCLUSION:Dexamethasone can cause dramatic changes in the gene expression profile in trabecular meshwork. The enriched pathways of DEGs and certain hub genes play an important role in the remodeling of the extracellular matrix and the regulation of aqueous humor outflow, providing a full knowledge of the molecular mechanism of GIG.