Oxidative stress in the trabecular meshwork – Preventive effects of Prostaglandin analogues

Abstract

Abstract Purpose: The trabecular meshwork (TM) of primary open angle glaucoma (POAG) is characterized by an increased accumulation of extracellular matrix, cellular senescence, and the loss of TM cells. One factor in the pathogenesis of POAG is oxidative stress. The goal of this study was to determine whether oxidative stress is able to trigger these POAG specific changes in cultured human TM cells and whether these changes could be reduced or prevented by the application of prostaglandin analogues (PA). Methods: Cultured human TM cells were stressed with hydrogen peroxide (H2O2) for 1 hour. Levels of fibronectin and MMP‐9 mRNA were analyzed by RT‐PCR. Senescence‐associated beta‐galactosidase (SA‐ß‐gal) activity was detected by histochemical staining. Cell loss was investigated by live dead assay. The effects of PA and benzalkonium chloride (BAC) on POAG typical TM changes were investigated by pre‐incubation with solutions of bimatoprost, travoprost and latanprost or its corresponding BAC concentrations of the either non stimulated or H2O2‐treated cells. Results: H202 markedly influenced the mRNA expression of fibronectin (1.8 fold), MMP‐9 (0.4 fold) and increased SA‐ß‐gal activity to 12 fold. Incubation with 600 μM H2O2 for induced 50% of dead cells. Pretreatment with BAC alone induced POAG typical TM changes in non‐stimulated and H2O2‐treated cells. These effects were reduced by preincubation with PA in H2O2‐treated cells and to a lesser extent in non stimulated cells. Conclusions: Oxidative stress is able to induce several characteristic POAG TM changes in vitro and these oxidative stress‐induced TM changes can be minimized by the use of PA. Thus, prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.