Abstract
Purpose:
We have evidence that the hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) can reduce intraocular pressure by increasing aqueous humor (AH) outflow facility via the conventional pathway. In the present study, we investigated the mechanism/s that underlie the NaHS-induced increase in AH outflow facility in porcine trabecular meshwork tissues ex vivo.
Methods:
Porcine ocular anterior segments explants with intact trabecular meshwork were perfused with Dulbecco’s Modified Eagle’s Medium maintained at 37° C, 5% CO2 and at constant pressure of 7.35 mmHg. Once outflow was stable (~3 hours), explants were exposed to an inhibitor of adenylyl cyclase, SQ22536 (100 µM), inhibitors of enzymes for H2S biosynthesis [proparglyglycine (PAG, 1 mM); aminooxyacetic acid (AOA, 30 µM)], and an inhibitor of cyclooxygenase (flurbiprofen, 3 µM), 30 minutes prior to application of NaHS (10 µM). Outflow was then monitored for an additional 4 hours, and vehicle control (0.1% saline) was run in parallel.
Results:
NaHS (10 µM) elicited a maximal effect [130.6 ± 10.51% of basal (mean ± SE)] on AH outflow facility. The NaHS-induced increase in AH outflow was attenuated by PAG and AOA by 56% and 79%, respectively. In the presence of flurbiprofen (3 µM), effects of NaHS on outflow was significantly (p <0.05) inhibited from [130.6 ± 10.51% of basal] to [102.9 ± 2.88% of basal]. Furthermore, the adenylyl cyclase inhibitor, SQ22536 completely blocked (p <0.05) the NaHS-induced increase in outflow facility.
Conclusions:
We conclude that the ability of NaHS to increase AH outflow in porcine trabecular meshwork is dependent upon the intramural generation of H2S and prostanoids, and on the integrity of the adenylyl cyclase pathway.<br /> <br />