The role of hydrogen sulfide in the retina

The discovery of the hydrogen sulfide (H₂S) and the transsulfuration pathway (TSP) responsible for its synthesis in the mammalian retina has highlighted this molecule's wide range of physiological processes that influence cellular signaling, redox homeostasis, and cellular metabolism. The multi-level regulatory program that influences H₂S levels in the retina depends on the relative expression and activity of TSP enzymes, which regulate the abundance of competitive substrates that support or abrogate H₂S synthesis. In addition, and apart from TSP, intracellular H₂S levels are regulated by mitochondrial sulfide oxidizing pathways. Retinal layers natively express differing levels of TSP enzymes, which highlight the differences in the metabolite and substrate requirement. Recent studies indicate that these systems are susceptible to pathophysiologies affecting the retina. Dysregulation at any level can upset the balance of redox and signaling processes and possibly upset oxidative stress, apoptotic signaling, ion channels, and immune response within this sensitive tissue. H₂S donors are a potential therapeutic in such cases and have been demonstrated to bridge the gap, positively impacting the damaged retina. Here, we review the recent findings of H₂S, how its multi-level regulation impacts the retina, and how its dysregulation is implicated in retinal pathologies.