Protective Effect Of H₂S On Oxidative Damage Induced By H₂O₂ And Heavy Ion Radiation In Human Retinal Pigment Epithelium Cells

Background:Age-related macular degeneration（AMD）is a common ophthalmic disease,mainly caused by functional degeneration of retinal pigment epithelium cells.The pathogenesis of AMD is closely related to oxidative stress,so oxidatively damaged human retinal epithelium cells ARPE-19 are often used as a cell model for simulating AMD.In order to building a cell model for simulating AMD in this study,H₂O₂ was used to induce oxidative damage and inflammatory response in ARPE-19 cells.Additionally,ARPE-19 cells were treated with heavy ion radiation as another model of cellular oxidative damage.The antioxidant and anti-inflammation roles of H₂S,a gas signal molecule,have been the focused area of research.H₂S donors are commonly used to transport H₂S gas molecules to targets more accurately.In this study,NaHS was used as the H₂S donor.Objective:This study was designed to investigate whether H₂S has protective effect against H₂O₂ and heavy ion radiation-induced oxidative damage in human retinal pigment epithelium cells.Results:（1）H₂O₂ caused cell viability inhibition,cell cycle arrest,and the increase of cell apoptosis and ROS level in ARPE-19 cells,whereas H₂S could protect cells against H₂O₂-induced oxidative damage.In addition,H₂O₂ induced the increased phosphorylation of AMPK,which could be inhibited by H₂S treatment.H₂S also inhibited H₂O₂-induced the production of MDA,and up-regulated antioxidant enzyme SOD level and small antioxidant molecule GSH level.Furthermore,H₂S could inhibit H₂O₂-induced the increased secretion level of inflammatory factors TNF-αand IL-1.（2）Heavy ion radiation could inhibit cell viability,and enhance cell apoptosis,ROS level and the secretion of related inflammatory factors TNF-αand IL-1 in ARPE-19 cells,while H₂S could effectively ameliorate heavy ion radiation-induced the inhibition of cell viability,and reduce cell apoptosis,ROS level and the secretion level of inflammatory factors TNF-αand IL-1 in ARPE-19 cells.In summary,two different conditions（H₂O₂ and heavy ion radiation）were used to establish oxidative damage models of human retinal pigment epithelium cells,and the study demonstrates H₂S has a good protective role against oxidative damage in human retinal pigment epithelium ARPE-19 cells.And its protective mechanism was investigated tentatively.This study could provide a preliminary theoretical basis for the prevention and treatment of AMD.