Effects of Hydrogen Sulfide-Releasing Compounds on Aqueous Humor Outflow Facility in Porcine Ocular Anterior Segments, Ex Vivo.

Abstract

To investigate the pharmacological actions of hydrogen sulfide (H2S)-releasing compounds l-cysteine and sodium hydrosulfide (NaHS) on aqueous humor (AH) outflow facility in porcine ocular anterior segment. Porcine ocular anterior segments were perfused with Dulbecco's modified Eagle's medium at a constant pressure of 7.35 mmHg. After stable outflow baseline, explants were exposed to NaHS or l-cysteine. The increase in outflow generated by the H2S-releasing compounds was measured in the absence and presence of inhibitor of H2S biosynthesis (aminooxyacetic acid; AOAA), blocker of KATP channels (glibenclamide), and inhibitor of adenylyl cyclase (SQ 22536). Hematoxylin and eosin (H&E) staining was used to assess trabecular meshwork (TM) morphology. l-cysteine elicited a concentration-dependent increase in AH outflow facility, reaching maximal effect at 100 nM (150.6% ± 17.2% of basal level). This increase in outflow induced by l-cysteine was significantly (P < 0.001) antagonized by AOAA (30 μM) and glibenclamide (100 μM). AOAA and glibenclamide had no significant action on baseline outflow, whereas SQ 22536 (100 μM) increased outflow for only an hour. In addition, NaHS produced a concentration-dependent increase in AH outflow, with a maximal effect at 10 μM (151.4% ± 22.9% of basal level). Likewise, the increase in outflow caused by NaHS was significantly (P < 0.04) blocked by glibenclamide and SQ 22536. H&E staining revealed that l-cysteine or NaHS did not alter TM conformation. H2S-releasing compounds can increase outflow facility in porcine ocular anterior segment. The stimulatory action of these compounds on outflow is mediated, in part by endogenously produced H2S, KATP channels, and adenylyl cyclase.