Abstract
Involvement of Katp channels in hydrogen sulfide‐induced increase in aqueous humor outflow Jenaye Robinson1, Chinoso Ezeudu1, Leah Mitchell1, Madhura Chitnis1, Catherine Opere2, Sunny E. Ohia1,Ya Fatou Njie‐Mbye1.
1Department of Pharmaceutical Sciences, College of Pharmacy and Health sciences, Texas Southern University, Houston TX 77004,2Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, NE 68178 We have evidence that hydrogen sulfide (H2S), a novel gasotransmitter can increase aqueous humor (AH) outflow in porcine trabecular meshwork tissues (TM). Purpose: To investigate the underlying mechanism of H2S‐induced increase in AH outflow. Methods: Porcine ocular anterior segment explants were perfused with DMEM maintained at 37ºC, 5% CO2 and constant pressure of 7.35 mmHg. Stabilized explants were exposed to the H2S‐releasing compound, sodium hydrosulfide (NaHS) and its substrate, L‐cysteine. Explants were also treated with the KATP channel antagonist glibenclamide and H2S biosynthetic enzyme inhibitors, aminooxyacetic acid (AOA), or proparglyglycine (PAG). Results: L‐cysteine (1 nM ‐ 1μM) caused a dose‐dependent increase in outflow, reaching a maximal effect at 100 nM [153 ± 7.2% of basal (mean ± SE)]. The effect of L‐cysteine (100 nM) on AH outflow was completely attenuated by AOA (30 μM) and PAG (1 mM). Interestingly, NaHS (100 nM ‐ 10 µM) also produced a concentration‐dependent increase in AH outflow, reaching a maximal effect at 10 μM. Furthermore, the enhancement of outflow caused by NaHS (10 μM) was inhibited significantly (p < 0.01) by glibenclamide (100 µM). Conclusions: We conclude that H2S‐induced increase AH outflow in porcine TM is dependent upon its intramural biosynthesis from L‐cysteine and, is mediated by KATP channels.
Grant Funding Source: Supported by NIH/NEI Grant R15EY022215