Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness.
• The specific molecular mechanisms underlying POAG pathogenesis remain incompletely understood.
• Trabecular meshwork (TM) dysfunction is implicated in the elevated intraocular pressure characteristic of POAG.

Purpose of the Study:

• To identify novel genes and pathways in the human TM associated with POAG.
• To investigate TM gene expression profiles in POAG patients, including those with MYOC mutations.
• To compare gene expression between POAG and control TM tissues.

Main Methods:

• Human TM specimens were collected from POAG surgical cases and non-glaucomatous donor eyes.
• RNA was extracted and hybridized to gene expression arrays (Illumina HumanWG-6 BeadChips).
• Differential gene expression analysis and pathway enrichment analyses were performed using bioinformatics tools.

Main Results:

• Analysis of 15 POAG and 13 control TM specimens identified 483 differentially expressed genes.
• Thirty-six of these genes were associated with TM exosomes, highlighting their potential role.
• Enriched functional clusters included cell adhesion, extracellular matrix, and secretion pathways.

Conclusions:

• This study represents the largest TM gene expression analysis in POAG to date.
• It is the first to report TM expression in a POAG patient with a Q368X MYOC mutation.
• Results suggest that endocytic and exosome-mediated pathways are potentially involved in POAG pathogenesis.