Identification of Optic Nerve–Related Biomarkers in Primary Open-Angle Glaucoma Based on Comprehensive Bioinformatics and Mendelian Randomization

Purpose: Glaucoma is the primary cause of permanent vision loss worldwide. However, the pathogenesis of primary open-angle glaucoma (POAG), the main type of glaucoma, has not yet been completely understood.

Methods: In our study, the POAG cohorts were obtained from the Gene Expression Omnibus (GEO) database (GSE45570). Biomarkers with diagnostic utility for POAG were identified through combining differentially expressed analysis, enrichment analysis, machine learning algorithms, and receiver operating characteristic (ROC) analysis. The regulatory networks (including a competing endogenous RNA (ceRNA) regulatory network and a small molecule compounds-mRNA network) were created. In addition, the Mendelian randomization (MR) analysis was used to identify exposures causally associated with POAG. Finally, the expression of the biomarkers was validated via realtime quantitative polymerase chain reaction (RT-qPCR).

Results: The Gene Ontology (GO) items that the differentially expressed genes (DEGs) between POAG and control groups enrichedwere relevant to light stimulation and DNA methylation. A total of three light stimulation-related biomarkers (RAB8A, PRG3, and SMAD3) were identified, which had diagnostic value for POAG patients. Besides, the ceRNA regulatory network contained 88 nodes and 93 edges, and a small molecule compounds-mRNA network included 66 nodes and 76 edges. The MR results indicated a causal association between DNA methylation GrimAge acceleration and POAG. Additionally, the results of RT-qPCR revealed that the expression trend of RAB8A was consistent with that of GSE45570.

Conclusions: Taken together, this study provides three light stimulation-related biomarkers (RAB8A, PRG3, andSMAD3) for the diagnosis of POAG, providing scientifically valuable insights for further studies of POAG.

*Author(s): Sijie Zhao ¹, QingDai ¹, Zixuan Rao ¹, ², Juan Li ¹, AiqinWang ¹, Ziqing Gao ¹, and Yuchen Fan ¹

1 Department of Ophthalmology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China
2 Bengbu Medical University, Bengbu, Anhui, China

Doi:10.1167/tvst.13.8.21

Experimental Paper of the Month manager: Rafael Correia Barão

Editors in Chief: Francesco Oddone, Manuele Michelessi