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

Abstract

Since our initial demonstrations that hydrogen sulfide (H₂S) may function as a neuromodulator in the brain and a smooth muscle relaxant in the vascular system, accumulating evidence shows that H₂S may function as a signaling molecule. We and others also found that H₂S has a cytoprotective effect. Because H₂S is well-known toxic gas, a cytoprotective role has been overlooked. H₂S protects neurons from oxidative stress. It also protects cardiac muscle from ischemia-reperfusion injury. The finding led to the application of H₂S to the bypass surgery patients in Phase II clinical trial. Cystathionine β–synthase (CBS) and cystathionine γ–lyase (CSE) are well known as H₂S-producing enzymes. We recently demonstrated that the other H₂S-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 H₂S production by 3MST/CAT pathway had not been well understood. The present study shows that H₂S production by 3MST/CAT pathway is regulated by Ca²⁺ and that H₂S protects retinal photoreceptor cells from light induced degeneration by suppressing excessive Ca²⁺ influx caused by intense light.

Keywords: :

• 3MST
• Ca²⁺
• CAT
• cytoprotective
• H₂S
• retina

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Acknowledgments

This work was supported by a grant from National Institute of Neuroscience and by KAKENHI (23659089) from Grant-in-Aid for Challenging Exploratory Research to H.K., by KAKENHI (23790316) from Grant-in-Aid for Young Scientists (B) to Y.M.