Identification of pathogenic genes and transcription factors in glaucoma

Glaucoma is a group of eye diseases characterized by alterations in the contour of the optic nerve head, with corresponding visual field defects and progressive loss of retinal ganglion cells. The present study aimed to identify the key genes and upstream regulators in glaucoma. To screen the pathogenic genes involved in glaucoma, an integrated analysis was performed by using the microarray datasets in glaucoma derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were additionally examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A glaucoma‑specific transcriptional regulatory network was constructed to identify crucial transcriptional factors that target the DEGs in glaucoma. From two GEO datasets, 1,935 DEGs (951 upregulated and 984 downregulated genes) between glaucoma and normal controls were identified. GO and KEGG analyses identified that 'eye development' [false discovery rate (FDR)=0.00415533] and 'visual perception' (FDR=0.00713283) were significantly enriched pathways for DEGs. The expression of lipocalin 2 (LCN2), monoamine oxidase A (MAOA), hemoglobin subunit β (HBB), paired box 6 (PAX6), fibronectin (FN1) and cAMP responsive element binding protein 1 (CREB1) were demonstrated to be involved in the pathogenesis of glaucoma. In conclusion, LCN2, MAOA, HBB, PAX6, FN1 and CREB1 may serve roles in glaucoma, regulated by PAX4, solute carrier family 22 member 1, hepatocyte nuclear factor 4 α and ELK1, ETS transcription factor. These data may contribute to the development of novel potential biomarkers, reveal the underlying pathogenesis and additionally identify novel therapeutic targets for glaucoma.