GSK3β Regualtes PVR Induced Epithelial-mesenchymal Transition

Background: Epithelial-mesenchymal transition(EMT)is a major pathological manifestation of PVR progression,the mechanism of which has not been fully elucidated.Glycogen Synthase Kinase-3β(GSK-3β)is a key protein that regulates the progress of EMT in some tumor growth and proliferation fibrosis diseases.In vitro experiments confirmed that GSK-3β is involved in the EMT of retinal pigment epithelial cells.However,the regulatory role of this cytokine in in vivo experiments is not yet clear.The purpose of this study was to investigate the regulatory mechanism of GSK-3β in the process of epithelial-mesenchymal transition in experimental PVR and further clarify the pathogenesis of PVR.Methods: Experimental PVR was induced by intravitreal injection of RPE cells in the eyes of rabbits.A PI3K/Akt inhibitor(Wortmannin)and a GSK-3β inhibitor(Li Cl)were also injected at different time during PVR progress.Electroretinagram(ERG),ocular fundus photographs,and B-scan ultrasonography were used to observe the PVR progress.Western blot test on the extracted retina were performed at 1,2,4 weeks.The expression of the mesenchymal markervimentin was determined by immunohistochemistry.Toxicity of WOR and Li Cl were evaluated by electroretinagramand TUNEL assay.The vitreous was also collected for metabolomic analysis.Results: Experimental PVR could significantly lead to epithelial mesenchymal transition(EMT),along with the suppressed expression of GSK-3β and the activation of Wnt/beta-catenin and PI3K/Akt pathways.It was verified that upregulating the expression of GSK-3β could effectively inhibit EMT process by suppressing Wnt/beta-catenin and PI3K/Akt pathways.Conclusions: GSK-3β effectively inhibits EMT via the Wnt/β-catenin and PI3K/Akt pathways.GSK-3β may be regarded as a promising target of experimental PVR inhibition.