AKR1B1‐Induced epithelial‐mesenchymal transision Mediated by RAGE‐ Oxidative Stress in the Lens of DM Cataracts

Abstract

Background and purposeCataracts in patients with diabetes are a major cause of blindness in developed and developing countries. It’s been known that lens epithelial cells (LECs) would undergo epithelial‐mesenchymal transision (EMT) that formed to cataract. Great deals of studies have demonstrated that overproduction of AKR1B1 and RAGE played a central role in the pathogenesis of diabetic cataract. The aim of this study was to examine whether EMT formation in the DM cataract through an AKR1B1 enhanced AGE and ROS generation in LECs from DM patients.MethodsFluorescence was used to estimate the AKR1B1, RAGE, AMPK and EMT biomarkers in the human lens epithelial sections from DM or non‐DM cataracts. All data were expressed as the mean ± SEM (n=12 for each group). A one‐way analysis of variance (ANOVA) with Scheffe’s post hoc comparison was employed to compare the group differences.ResultsImmunohistochemistry staining founding that the pathologic phases and N‐cadherin expression levels were significantly enhanced in the human lens epithelial sections from DM (+) than DM (−) cataract patients. Immunofluorescent staining also demonstrated that AKR1B1 and RAGE were significantly enhanced in the human lens epithelial sections from DM (+) than DM (−) cataract patients. Interestingly, AcSOD2 levels were significantly higher in the LECs of the patients with DM, not in non‐DM cataracts, however, the phosphorylation level of AMPKT172 was has reverse effect. These results indicated that AMPKT172 may be required for reduced superoxide generation and the pathogenesis of diabetic cataract formation.ConclusionsCollectively, our results revealed that AKR1B1 overexpression would abolish AMPK activation, thereby increasing AcSOD2 and RAGE‐induced EMT formation in the LECs of diabetic cataracts as potentially important elements in the pathogenesis of diabetic cataract.Support or Funding Information108‐2320‐B‐075B‐002 ‐