Canagliflozin Inhibits NLRP3 Inflammasome Activation In Retinal Vein Occlusion

Objective:In this study,we will investigate whether Canagliflozin has a protective effect on retinal vein occlusion(RVO)by inhibiting NLRP3 inflammasome activation.Methods:(1)Laser-induced RVO model in C57BL/6J mice were administrated with diet containing Canagliflozin.The experimenta mice were divided into Vehicle+No-RVO group,Vehicle+RVO group,Canagliflozin+No-RVO group and Canagliflozin+RVO group;(2)Fundus Fluorescein Angiography(FFA)was used to detect the formation of retinal nonperfusion(RNP).The activation of microglia cells and loss of retinal ganglion cells(RGCs)were determined by retinal flat-mount immunofluorescence staining.The activation of Müller glial cells was examined with immunofluorescence staining of retinal cryosections.The death of RGCs was examined with TUNEL staining of retinal cryosections.The expression of inflammatory cytokines and activation of NLRP3 inflammasome were detected by western blot analysis.Results:(1)Canagliflozin has a protective effect on the retina in RVO independent of glycemic control and weight control;(2)Canagliflozin alleviated RNP formation and inhibited the expression of HIF-1α,VEGF,ICAM-1,and leakage of Albumin,as well as suppressed retinal glial cell activation and RGCs loss in RVO mice;(3)Canagliflozin played a protective role in RVO mice,possibly by inhibiting the activation of NLRP3 inflammasome.Conclusions:Canagliflozin inhibited the inflammatory response and played a protective role by inhibiting the activation of NLRP3 inflammasome in the retina of RVO mice.