Effects of hydrogen peroxide-induced oxidative damage on outflow facility and washout in pig eyes

Previous studies show that hydrogen peroxide (H2O2) is present in the aqueous humor of many species and is capable of affecting outflow facility in animal model experiments. To study the hypothesis that oxidative damage to the outflow pathway may play a role in the pathogenesis of primary open-angle glaucoma, 3 mM H2O2 with 20 mM 3-aminotriazole and 1 mM carmustine (BCNU) in Dulbecco's phosphate-buffered saline (DPBS) was perfused into enucleated pig eyes at constant pressure. Baseline and experimental perfusions were done at two different pressures (7.5 and 30 mm Hg) to study the effect of pressure on the response to oxidative damage. Outflow facility in the baseline experiments (with DPBS only) was observed to increase nonlinearly with time during the perfusions, but could be linearized if plotted as a function of the volume perfused. Thus, a term "volumetric washout" (W) was introduced and defined as the fractional rate of change of outflow facility with respect to the volume perfused. This quantity was found to be independent of pressure in the baseline studies. Perfusion of H2O2 and inhibitors increased W at 7.5 mm Hg but decreased W at 30 mm Hg. These results indicate that oxidative damage increases outflow facility at normal pressure but decreases it at elevated pressure, suggesting that elevated pressure may increase the susceptibility of the outflow pathway to this form of insult.