From Load-Bearing Tissue to Failed Filter: A Conceptual Framework for Trabecular Meshwork Breakdown in...

Pseudoexfoliation glaucoma (PXG) is a unique cause of open-angle glaucoma with a more severe clinical course and higher intraocular pressure (IOP) than primary open-angle glaucoma (POAG). This reflects progressive structural failure of the trabecular meshwork (TM) driven by pseudoexfoliation (PXF) fibrillar material deposition, distinguishing PXG from POAG pathogenically. The TM, an active load-bearing filtration sieve, regulates IOP and is most affected by XFM deposition and extracellular matrix (ECM) dysregulation in PXG. Despite extensive research, the mechanism of trabecular dysfunction remains unclear, with both mechanical obstruction and ischemic/oxidative stress implicated. This narrative review amalgamates evidence across TM biology, PXF material science, and glaucoma pathophysiology to propose a five-stage framework for TM failure in PXG.