Effects of Oxidative Stress in Trabecular Meshwork Cells Are Reduced by Prostaglandin Analogues

PURPOSE. The trabecular meshwork (TM) of glaucomatous eyes is characterized by cell loss, increased accumulation of extracellular matrix (ECM), and cellular senescence. One factor increasingly discussed in the pathogenesis of primary open-angle glaucoma (POAG) is oxidative stress. The goal of this study was to determine whether oxidative stress is able to trigger these typical glaucomatous changes in vitro and whether these oxidative stress-induced TM changes can be reduced by the application of prostaglandin analogues. METHODS. Cultured human TM cells were exposed to 200 to 800 mu M hydrogen peroxide (H2O2) for 1 hour. Cell loss was detected by cell-viability assay. Levels of fibronectin and MMP-2 mRNA were determined by real-time PCR analysis. Senescence-associated beta-galactosidase (SA-beta-Gal) activity was investigated by histochemical staining. The effects of prostaglandin analogues and benzalkonium chloride (BAC) on these glaucoma typical TM changes were investigated by preincubation of nonstressed or H2O2-treated cells with 1:100 diluted commercial solutions of bimatoprost, travoprost, and latanoprost or their corresponding BAC concentrations. RESULTS. H2O2 induced cell death and fibronectin mRNA expression, but decreased the amount of MMP-2 mRNA. H2O2 increased (SA-beta-Gal) activity. Additional pretreatment with BAC further increased the typical glaucomatous TM changes in vitro. These effects were reduced by preincubation with prostaglandin analogues in H2O2-treated and, to a lesser extent, in nonstressed cells. No reduction occurred in the presence of prostaglandin F receptor antagonists in H2O2-treated cells. CONCLUSIONS. Oxidative stress is able to induce characteristic glaucomatous TM changes in vitro, and these oxidative stress induced TM changes can be minimized by the use of prostaglandin analogues. Thus, prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG. ( Invest Ophthalmol Vis Sci. 2008;49:4872-4880) DOI: 10.1167/iovs.07-0984