Abstract
Purpose:
Hydrogen sulfide (H2S) is a gasotransmitter with demonstrated pharmacological actions in mammalian ocular tissues. We have evidence that inhibitors of the cyclooxygenase (COX) pathway such as flurbiprofen can enhance the pharmacological effects of H2S in the mammalian anterior uvea and retinae. However, it remains to be determined whether this gas can directly regulate the biosynthesis of prostanoids such as prostaglandin E2 (PGE2) in isolated irides and retinae. In the present study, we examine the effect of H2S on the intramural generation of PGE2 in the isolated bovine irides and neural retina.
Methods:
Isolated bovine irides and retinae were incubated in warm oxygenated Krebs buffer for 30 minutes and subsequently exposed to different concentrations of H2S-releasing compounds, L-cysteine and sodium hydrosulfide (NaHS). After incubation, tissues were homogenized and both homogenates and incubation media were collected and prepared for prostaglandin E2 (PGE2) Enzyme-Immunoassay using a well-established methodology.
Results:
Retinal tissues treated with NaHS (1 nM - 10 µM) exhibited a significant (p < 0.01) increase in basal PGE2 levels with the maximum effect achieved at 10 nM. Furthermore, there was a concentration-dependent increase in PGE2 concentrations in the incubation media of retinae treated with NaHS (10 nM - 100 µM). L-cysteine (1 nM - 10 µM) also caused a significant (p < 0.01) concentration-dependent increase in PGE2 production in the retina. However, there was no significant increase in PGE2 production in the incubation media containing retinal tissues that were treated with L-cysteine. In bovine isolated irides, L-cysteine (10 nM - 10 µM) caused a concentration-dependent increase in PGE2 levels in both tissues and the incubation media. The positive control, norepinephrine (1 µM) also caused an increase in PGE2 over basal levels in ocular tissues.
Conclusions:
H2S (using L-cysteine and NaHS as donors) can increase the endogenous biosynthesis of PGE2 in isolated bovine irides and neural retina, indicating a role for prostanoids in pharmacological actions of this gas in the eye.<br />