Hydrogen Sulfide Protects Primary Retinal Ganglion Cells from Hypoxic Damage through the Activation of KATP Channels

Abstract

Background: Retinal ganglion cells (RGCs) affected by ischemia cause irreversible visual impairment. Hydrogen sulfide (H₂S) may protect RGC-5 from oxidative damage by increasing glutathione levels. This study aimed to evaluate the ability of H₂S to reduce oxygen-glucose deprivation (OGD)-induced apoptosis in RGC cells by activating ATP-sensitive potassium (K_ATP) channels. Methods: First, purified primary RGCs were cultured and treated with OGD or OGD + NaSH. Cell mortality was observed through Hoechst-33258 staining and enzymatic immunoassay. Then, the RGCs were treated with pinacidil or glibenclamide (ATP-sensitive potassium channel agonist or inhibitor) to observe whether H₂S protects against OGD-induced cell damage through activation of ATP-sensitive potassium channels using patch clamp, immunoblot and calcium imaging techniques. Results: Under OGD, apoptotic cell death was effectively prevented by NaSH. Simultaneous treatment with 300 μM NaSH and OGD exposure delayed cell death. H₂S protected RGCs at an early stage after OGD and delayed the start of OGD injury. Resting potential (RP) was significantly hyperpolarized after NaSH or pinacidil exposure compared to vehicle (p < 0.05). Hyperpolarization due to NaSH was induced by the activation of K_ATP channels. RGCs apoptosis induced by OGD was suppressed by H₂S through the activation of the K_ATP channel. Conclusion: H₂S reduced calcium efflux and prevented OGD-induced neuronal death in primary RGCs, and the neuroprotective effect of H₂S was associated with the activation of K_ATP channels.