LncRNA-MALAT1 Promotes Ganglion Cell Death In Ischemia Reperfusion Mice

Objective:Acute retinal ischemia/reperfusion(I/R)is one of the common pathological processes in acute ocular hypertension glaucoma,resulting in the irreversible damage and death of retinal ganglion cells(RGCs).However,its specific molecular mechanism remains unclear.Thus,the purpose of this study was to investigate the role of long non-coding RNA(lnc RNA-MALAT1)in retinal acute I/R injury of mice,and to clarify the regulatory role of MALAT1 in microglial pyroptosis and RGCs death.Methods: We construct a mouse model for acute retinal I/R.MALAT1 and pyroptosisrelated molecules were detected using real-time fluorescence quantitative polymerase chain reaction(RT-q PCR),western blotting and immunofluorescence.MALAT1 expression was knocked down with the retinal transfection of adeno-associated virus(AAV),which was injected into the vitreous cavity.Retinal structure,morphology and function of RGCs and microglia were then evaluated by HE staining,TUNEL,retinal immunofluorescence and flare-visional Evoked Potential(F-VEP).Results: The expressions of MALAT1 and pyroptosis-related proteins(NLRP3,Caspase-1,N-GSDMD,and IL-18)expression were increased in the retina of I/R mice.Consequently,the retina became thinner,and the number of RGCs decreased.The number of microglia increased,as the morphology changed from a resting to an active state,and the co-contamination results of IBA1 and N-GSDMD showed increased microglia pyroptosis.Furthermore,the P2 wave latency of F-VEP was prolonged.On knocking down MALAT1,reduction of I/R-induced MALAT1 elevation,inhibition of pyroptosis related protein expression,reduction of RGC loss and inhibition of microglial activation and pyroptosis were observed.In addition,knocking down MALAT1 increased the overall retinal thickness of I/R mice and shortened the P2 wave latency of F-VEP.Conclusion: Acute retinal ischemia-reperfusion can lead to loss of RGCs and activation of microglia.The abnormal increase of MALAT1 promotes optic nerve inflammation by inducing microglia pyroptosis,which leads to the death of RGCs.MALAT1 knockdown with AAV transfection can effectively inhibit microglia pyroptosis and optic nerve inflammation following an acute I/R injury,thereby reducing the loss of RGCs.