Roles of Prostaglandins and Hydrogen Sulfide in an Outflow Model of the Porcine Ocular Anterior Segment Ex Vivo.

BACKGROUND

Hydrogen sulfide (HS)-releasing compounds can reduce intraocular pressure in normotensive rabbits by increasing aqueous humor (AH) outflow through the trabecular meshwork. In the present study, we investigated the contribution of endogenous HS and the role of intramurally generated prostaglandins in the observed increase in AH outflow facility in an ex vivo porcine ocular anterior segment model.

MATERIAL AND METHODS

Porcine ocular anterior segment explants were perfused with Dulbecco's Modified Eagle's Medium maintained at 37 °C and gassed with 5% CO and 95% air under an elevated pressure of 15 mmHg for four hours. Perfusates from the anterior segment explants were collected and immediately assayed for their HS and prostaglandin E content.

RESULTS

Elevating perfusion pressure from 7.35 to 15 mm Hg significantly ( < 0.001) increased HS concentration in the perfusate from 0.4 ± 0.1 to 67.6 ± 3.6 nM/µg protein. In the presence of an inhibitor of cystathionine ß-synthase/cystathionine γ-lyase, aminooxyacetic acid (AOAA, 30 µM), or an inhibitor of 3-mercaptopyruvate sulfurtransferase, α-ketobutyric acid (KBA, 1 mM), the effects of elevated pressure on HS levels in the perfusate was significant ( < 0.001). Furthermore, flurbiprofen (30 µM) and indomethacin (10 µM) attenuated the elevated pressure-induced increase in HS levels in the perfusate. Interestingly, elevating perfusion pressure had no significant effect on PGE concentrations in the perfusate. While the inhibition of HS biosynthesis by AOAA or KBA did not affect PGE levels in perfusate, flurbiprofen (30 µM) caused a significant ( < 0.05) decrease in the concentration of PGE under conditions of elevated perfusion pressure.

CONCLUSIONS

We conclude that the elevated perfusion pressure-induced increase in HS concentrations depends upon the endogenous biosynthesis of HS and intramurally produced prostaglandins in the porcine anterior segment explants. While the concentration of PGE in the perfusate under elevated perfusion pressure was unaffected by pretreatment with inhibitors of HS biosynthesis, it was reduced in the presence of an inhibitor of cyclooxygenase.