A mechanism of retinal protection from light-induced degeneration by hydrogen sulfide

Since our initial demonstrations that hydrogen sulfide (H(2)S) may function as a neuromodulator in the brain and a smooth muscle relaxant in the vascular system, accumulating evidence shows that H(2)S may function as a signaling molecule. We and others also found that H(2)S has a cytoprotective effect. Because H(2)S is well-known toxic gas, a cytoprotective role has been overlooked. H(2)S protects neurons from oxidative stress. It also protects cardiac muscle from ischemia-reperfusion injury. The finding led to the application of H(2)S to the bypass surgery patients in Phase II clinical trial. Cystathionine β–synthase (CBS) and cystathionine γ–lyase (CSE) are well known as H(2)S-producing enzymes. We recently demonstrated that the other H(2)S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) is localized to neurons in the brain and to the vascular endothelium. However, the regulation of H(2)S production by 3MST/CAT pathway had not been well understood. The present study shows that H(2)S production by 3MST/CAT pathway is regulated by Ca(2+) and that H(2)S protects retinal photoreceptor cells from light induced degeneration by suppressing excessive Ca(2+) influx caused by intense light.