Transcriptomic and regulatory gene associations in open angle glaucoma
Reviewed by Ian Reekie

The authors report a study utilising a publicly available whole exome sequencing dataset of 28 patients with primary open angle glaucoma (POAG) and seven healthy control patients, and a transcriptomic dataset from the trabecular meshwork of four POAG patients and four healthy controls. It is not expressly stated, but the transcriptomic data appears to be from bulk RNA sequencing. The initial analysis of the whole genome sequencing data identifies potentially pathogenic variants in 46 genes, but of note the study uses p<0.05 as the cut off for statistical significance rather than the more stringent values which are more common in many genome-wide association studies. Comparison of the transcriptomic datasets from POAG and healthy trabecular meshwork identifies differentially expressed genes, either upregulated or downregulated in the POAG group. These are then mapped to functional pathways, annotated by gene ontology terms and other databases of gene functions. This section identified some interesting pathways connected to the differentially expressed genes, many of which are immunological in nature, e.g. phagocytosis, IgA synthesis and T-cell differentiation. The final section of work attempts to incorporate the identified pathogenic gene mutations along with the differentially expressed genes to produce a competing endogenous RNA (ceRNA) network analysis, highlighting that regulatory RNAs may play a role in POAG pathogenesis. Currently however the clinical utility of this last section is extremely limited, and the transcriptomic analysis indicating the role of inflammatory pathways in POAG remains the most immediately interesting part of this study.

Identification of regulatory genes associated with POAG by integrating expression and sequencing data.
Wang X, Zhang Q, Zhao D, et al.
OPHTHALMIC GENETICS
2025;46(1):56–64.