The Molecular Mechanisms of Trabecular Meshwork Damage in POAG and Treatment Advances

Abstract

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness affecting over 60 million people worldwide. Elevated intraocular pressure (IOP) due to dysfunction of trabecular meshwork (TM) is the most significant and the only known modifiable risk factor for POAG. Although, glaucomatous TM damage is known to be mainly responsible for IOP elevation, none of the current treatments target TM pathology. This is partly due to an incomplete understanding of the pathophysiological mechanisms of TM damage. In this review, we summarized pathological changes of TM damage in POAG and our current knowledge of the mechanisms of glaucomatous TM damage, particularly focusing on linking the genetic factors of POAG (e.g., mutations and variants in POAG risk genes, risk loci, dysregulation of gene expression) to molecular pathways of pathogenesis in TM. In terms of treatment, reduction of IOP is the mainstream strategy that can be achieved by medical, laser or surgical treatment. IOP lowering drugs, laser or surgery can lower IOP, but do not reverse or restore the oxidative stress or other TM damage in POAG. Additionally, antioxidants, ginkgo biloba extract and nutrients could be a promising treatment for POAG.