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

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.