Hydrogen sulfide: a gaseous signaling molecule modulates tissue homeostasis: implications in ophthalmic diseases

Abstract

Hydrogen sulfide (H 2 S) serves as a gasotransmitter in the regulation of organ development and maintenance of homeostasis in tissues. Its abnormal levels are associated with multiple human diseases, such as neurodegenerative disease, myocardial injury, and ophthalmic diseases. Excessive exposure to H 2 S could lead to cellular toxicity, orchestrate pathological process, and increase the risk of various diseases. Interestingly, under physiological status, H 2 S plays a critical role in maintaining cellular physiology and limiting damages to tissues. In mammalian species, the generation of H 2 S is catalyzed by cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), 3-mercapto-methylthio pyruvate aminotransferase (3MST) and cysteine aminotransferase (CAT). These enzymes are found inside the mammalian eyeballs at different locations. Their aberrant expression and the accumulation of substrates and intermediates can change the level of H 2 S by orders of magnitude, causing abnormal structures or functions in the eyes. Detailed investigations have demonstrated that H 2 S donors’ administration could regulate intraocular pressure, protect retinal cells, inhibit oxidative stress and alleviate inflammation by modulating the function of intra or extracellular proteins in ocular tissues. Thus, several slow-releasing H 2 S donors have been shown to be promising drugs for treating multiple diseases. In this review, we discuss the biological function of H 2 S metabolism and its application in ophthalmic diseases.

Characterization of hydrogen sulfide toxicity to human corneal stromal fibroblasts

“…We also identified factors and pathways contributing to H 2 S toxicity to the human cornea. In the eye, low endogenous quantities of H 2 S have beneficial effects 20,[25][26][27][28][29][30][31][32] but high H 2 S levels have toxicological effects. 10,13,[33][34][35] The utilized toxicological assays demonstrated that H 2 S toxicity to hCSFs is dose and time dependent (Figs.…”

“…Sodium hydrosulfide (NaSH) (Sigma-Aldrich) powder, which produces H 2 S gas after addition to media, was used for studying H 2 S-induced toxicity. 20,21 The hCSFs were grown in T25 tissue culture flasks to 80-85% confluence and were treated with different concentrations of NaSH (1-10 mM) in a serum-free environment for up to 72 hours. Immediately after adding NaSH, the T25 culture flasks were sealed with plug-seal caps to prevent the leakage of H 2 S gas.…”

“…H 2 S is also generated endogenously in the gastrointestinal, brain, liver, heart, and ocular tissues. [14][15][16][17][18][19][20] In humans, the gut microbiota produces endogenous H 2 S by metabolizing sulfhydryl-containing amino acids. [14][15][16] In the mammalian brain, liver, and heart, endogenous H 2 S is produced by various enzymes: cystathionine beta-synthase, cystathionine gamma-lyase, 3-mercaptopyruvate sulfurtransferase, and cysteine aminotransferase.…”

“…24 The endogenous concentrations of H 2 S are beneficial to ocular tissues and contribute to tissue homeostasis. 20 Deficiency of endogenous H 2 S or its substrates is associated with several pathologies, including cataracts, ectopia lentis, myopia, optic atrophy, and retinal detachment. [25][26][27][28] Treatment with H 2 S donors shows positive effects in regulating intraocular pressure (IOP), and anti-inflammatory and antioxidative properties in the eye.…”

Emerging medical therapies in crush syndrome – progress report from basic sciences and potential future avenues

“…Hydrogen sulfide (H 2 S) is a newly discovered gas signal molecule which is generated in the human body [68]. Low concentration of H 2 S plays a role in relaxing blood vessels, controlling blood pressure and maintaining homeostasis [69,70].…”