Potential role of lysosomal dysfunction in the pathogenesis of primary open angle glaucoma

Primary open angle glaucoma (POAG) is a late onset disease usually accompanied by elevated intraocular pressure (IOP) that results from the failure of the trabecular meshwork (TM) to maintain normal levels of aqueous humor outflow resistance. Cells in the TM are subjected to chronic oxidative stress through reactive oxygen species (ROS) present in the aqueous humor (AH) and generated by normal metabolism. Exposure to ROS is thought to contribute to the morphological and physiological alterations of the outflow pathway in aging and POAG. Our results indicate that chronic exposure of TM cells to oxidative stress causes the accumulation of nondegradable material within the lysosomal compartment leading to diminished lysosomal activity and increased SA-β-Gal expression. Because the lysosomal compartment is responsible for maintaining general cellular turnover, such impaired activity may lead to a progressive cellular decline in the TM cell function and thus contribute to the progression of POAG.