Background: We have evidence that hydrogen sulfide (H
2S)-releasing compounds can reduce intraocular pressure in normotensive and glaucomatous rabbits by increasing the aqueous humor (AH) outflow through the trabecular meshwork. Since H
2S has been reported to possess neuroprotective actions, the prevention of retinal ganglion cell loss is an important strategy in the pharmacotherapy of glaucoma. Consequently, the present study aimed to investigate the neuroprotective actions of H
2S-releasing compounds against hydrogen peroxide (H
2O
2)-induced oxidative stress in an isolated bovine retina.
Materials and Methods: The isolated neural retinae were pretreated with a substrate for H
2S biosynthesis called L-cysteine, with the fast H
2S-releasing compound sodium hydrosulfide, and with a mitochondrial-targeting H
2S-releasing compound, AP123, for thirty minutes before a 30-min oxidative insult with H
2O
2 (100 µM). Lipid peroxidation was assessed via an enzyme immunoassay by measuring the stable oxidative stress marker, 8-epi PGF2α (8-isoprostane), levels in the retinal tissues. To determine the role of endogenous H
2S, studies were performed using the following biosynthesis enzyme inhibitors: aminooxyacetic acid (AOAA, 30 µM); a cystathione-β-synthase/cystathionine-γ-lyase (CBS/CSE) inhibitor, α–ketobutyric acid (KBA, 1 mM); and a 3-mercaptopyruvate-s-sulfurtransferase (3-MST) inhibitor, in the absence and presence of H
2S-releasing compounds.
Results: Exposure of the isolated retinas to H
2O
2 produced a time-dependent (10–40 min) and concentration-dependent (30–300 µM) increase in the 8-isoprostane levels when compared to the untreated tissues. L-cysteine (10 nM–1 µM) and NaHS (30 –100 µM) significantly (
p < 0.001; n = 12) prevented H
2O
2-induced oxidative damage in a concentration-dependent manner. Furthermore, AP123 (100 nM–1 µM) attenuated oxidative H
2O
2 damage resulted in an approximated 60% reduction in 8-isoprostane levels compared to the tissues treated with H
2O
2 alone. While AOAA (30 µM) and KBA (1 mM) did not affect the L-cysteine evoked attenuation of H
2O
2-induced oxidative stress, KBA reversed the antioxidant responses caused by AP123.
Conclusions: In conclusion, various forms of H
2S-releasing compounds and the substrate, L-cysteine, can prevent H
2O
2-induced lipid peroxidation in an isolated bovine retina.
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