Characterizing the "POAGome": A bioinformatics-driven approach to primary open-angle glaucoma.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Primary open-angle glaucoma (POAG) is a complex neurodegenerative disease with a multifactorial etiology.
• The genetic landscape of POAG is continually expanding, necessitating comprehensive analysis of known associated genes.

Purpose of the Study:

• To systematically compile and analyze genes associated with POAG and related ocular conditions.
• To elucidate the molecular pathways and biological processes underlying POAG pathogenesis.
• To propose a novel molecular model for POAG incorporating key identified pathways.

Main Methods:

• Bioinformatics tools were employed for a systematic literature search to identify POAG-associated genes.
• Compiled 542 genes linked to POAG and its phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, primary congenital glaucoma).
• Functional annotation and pathway analyses were performed on the compiled gene set, classifying genes by ocular tissue and phenotype.

Main Results:

• No single molecular pathway fully explains POAG pathophysiology.
• Inflammation and senescence emerged as critical factors in retinal ganglion cell degeneration.
• The TGF-β signaling pathway was consistently implicated across analyses, suggesting a central role in POAG manifestation.

Conclusions:

• POAG pathogenesis is complex, involving multiple interacting pathways.
• A molecular model centered on TGF-β signaling, integrating inflammation and senescence, is proposed for POAG.
• Emerging molecular therapies targeting these pathways show promise for future POAG treatment.