Identification of a chromatin regulator signature and potential candidate drugs for primary open-angle glaucoma.

Abstract

Aims: This research aims to establish a chromatin regulator (CR) signature to provide new epigenetic insights into the pathogenesis of primary open-angle glaucoma (POAG).

Materials & methods: The expression profile of CRs in trabecular meshwork (TM) tissues was analyzed by bioinformatics analysis; The selected hub CRs were further verified by cell experiments.

Results: We found the immune microenvironment of the TMwas changed in POAG patients and identified 3 differentially expressed CRs that were relevant to immunity. Then, we successfully constructed and proved a predicted signature based on these 3 CRs, which could effectively predict the risk of POAG. The genes co-expressed with these 3 CRs and miRNAs with are gulatory relationship were identified, and a miRNA-hub CR network was successfully constructed. The results of the Gene Set Enrichment analysis indicated that these 3 hub CRs were all associated with neurodegenerative diseases. Moreover, the human trabecular meshwork cell (HTMC) oxidative stress model was constructed, and KDM5B was significantly down-regulated in this cell model. Finally, we found 10 agents that might be helpful for patients with POAG.

Conclusions: Dysregulation of CR expression in TM tissues may be involved in the occurrence and progression of POAG through multiple mechanisms.