Neuroprotective and anti-inflammatory effects of eicosane on glutamate and NMDA-induced retinal ganglion cell injury

AIM:To investigate the protective effects,antioxidant potential,and anti-inflammatory mechanisms of eicosane on glutamate-induced cell damage and on N-methyl-Daspartate(NMDA)-induced retinal ganglion cell(RGC)injury in a mouse model of glaucoma.METHODS:The protective effects of eicosane on the rat R28 retinal precursor cell line were assessed using cell counting kit-8 assays and Hoechst-propidium iodide staining.Intracellular reactive oxygen species(ROS)production was measured using the fluorescent probe 2'-7'-dichlorofluorescin diacetate and flow cytometry.The protective role of eicosane on NMDA-induced RGC injury in a mouse glaucoma model was determined by immunostaining of frozen sections of retina.The effects of eicosane on the metabolome of the retina in mice with NMDA-induced RGC damage were evaluated by liquid chromatographymass spectroscopy(LC-MS)and untargeted metabolomics analyses.RESULTS:Eicosane treatment significantly attenuated glutamate-induced damage to R28 cells in vitro.Eicosane also protected RGCs against NMDA-induced injury in a mouse glaucoma model.Untargeted metabolomics analyses showed that eicosane increased multiple metabolites,including L-arginine and L-carnitine,in the retina.CONCLUSION:Eicosane has protective effects,antioxidant potential,and anti-inflammatory properties in an in vitro model of glutamate-induced cell damage and in an in vivo model of NMDA-induced RGC injury in mouse glaucoma through modulation of L-arginine and/or L-carnitine metabolism.