Although primary open-angle glaucoma (POAG) is the leading cause of blindness in people over the age of 55, there remains no cure for the disease and its biological mechanisms are not well understood. Elevated intraocular pressure (IOP) is a major risk factor for the disease, but many patients with glaucoma have normal eye pressure and still lose vision.
In a new study, researchers from Mass Eye and Ear conducted a comprehensive study that combined genetic discoveries from a large cross-ancestry genome-wide association study meta-analysis of POAG with a large meta-analysis of IOP with genetic regulation studies and single cell expression measurements in glaucoma-relevant eye tissues. In doing so, they uncovered key genes, biological processes and cell types that may affect the pathogenesis of POAG, in IOP-dependent and independent manners.
Using integrative analyses, they identified hundreds of genes and regulatory effects underlying over 100 loci associated with POAG and/or IOP that may contribute to glaucoma risk through altered gene expression levels. These genes are enriched in biological pathways implicated in disease mechanisms, including elastic fiber formation and extracellular matrix organization, vascular development, and neuronal related processes.
Pathways identified in their analysis can impact various structures in the eye, pointing to numerous potential mechanisms that can interact with different genes and cell types that may contribute to POAG. These findings provide new insights regarding gene expression and post-transcriptional gene regulation that could improve drug design for glaucoma.