AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3 beta (GSK3 beta) in epithelial-mesenchymal transition (EMT) process after proliferative vitreoretinopathy (PVR) induction.
METHODS: Experimental PVR was induced by intravitreal injection of retinal pigment epithelium (RPE) cells in the eyes of rabbits. A PI3K/Akt inhibitor (wortmannin) and a GSK3 beta inhibitor (LiCl) were also injected at different time during PVR progress. Electroretinogram (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, 4wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and LiCl were evaluated by ERG and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The vitreous was also collected for metabolomic analysis.
RESULTS: Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3 beta and the activation of Wnt/beta-catenin and PI3K/Akt pathways. It was verified that upregulating the expression of GSK3 beta could effectively inhibit EMT process by suppressing Wnt/beta-catenin and PI3K/Akt pathways.
CONCLUSION: GSK3 beta effectively inhibits EMT via the Wnt/beta-catenin and P13K/Akt pathways. GSK3 beta may be regarded as a promising target of experimental PVR inhibition.
[1]Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Ophthalmol,Shanghai Gen Hosp, Shanghai 200000, Peoples R China.
[2]Shanghai Key Lab Fundus Dis, Shanghai 200000, Peoples R China.
[3]Shanghai Engn Ctr Visual Sci & Photomed, Shanghai 200000, Peoples R China.
[4]Shanghai Univ Tradit Chinese Med, Shanghai Shuguang Hosp, Dept Ophthalmol, Shanghai 200000, Peoples R China.
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