Nmnat1: A Security Guard Of Retinal Ganglion Cells (RGCs) In Response To High Glucose Stress

Objective:This study aims to investigate the role of Nmnatl in high glucose-induced RGC injury.Methods:1.Western blot and immunoflouresence were conducted to detect Nmnatl expression pattern in the retina of rat,mouse and RGC.2.Building high glucose models using RGC.The experiment included five groups:normal group,Nmnatl knockdown group,30 mmol/L glucose treatment group,Nmnatl nockdown with 30 mmol/L glucose treatment group,and scrambled siRNA knockdown with 30 mmol/L glucose treatment group.MTT assay,Hoechst staining,trypan blue staining,and calcein-AM/propidium iodide(PI)staining were conducted to determine the cell viability and apoptosis of Nmnatl knockdown on RGC function.3.Microarray and bioinformatics analysis were conducted to identify potential signaling pathways affected by Nmnatl knockdown.4.Pharmacological intervention,molecular intervention,and in vitro experiments were conducted to reveal molecular mechanism of Nmnatl-mediated protective effect on RGC function.Results:1.Nmnatl is constitutively expressed in retina of rat,mouse and RGC.2.High glucose stress aggravates RGC injury.The cell viability of RGC was further decreased,the cell apoptosis and death were further increased after Nmnatl Knockdown.3.MAPK signaling is the primary signaling pathway affected by Nmnat 1 knockdown.4.Under high glucose stress,Nmnatl knockdown leads to p38-MAPK signaling inactivation.p38-MAPK pathway inhibitor SB203580 strongly blocks Nmnatl-mediated protective effect on RGC function.Conclusion:Nmnatl protects RGC against high glucose-induced injury via p38-MAPK signaling pathway.Nmnat1 may serve as a neuroprotective target for diabetes mellitus-related retinal neuropathy.