Nuclear Translocation Of Beta-Catenin Induced By E-Cadherin Endocytosis Causes Recurrent Erosion Of Diabetic Cornea

Recurrent epithelial erosion and refractory corneal ulcer are the clinical features of diabetic keratopathy (DK), which eventually lead to corneal scar and visual disturbance. In this study, we sought to determine the abnormalities of cell junction in diabetic corneal epithelial cells and the effect of high glucose on the beta-catenin/E-cadherin complex. Corneal histology showed that corneal epithelial cells of high glucose mice were loosely arranged, and the immunohistochemistry showed that the expression of E-cadherin decreased, the levels of beta-catenin increased in nuclear. High glucose-induced degradation and endocytosis of E-cadherin of corneal epithelial cells reduce the formation of beta-catenin/E-cadherin complex and promote the nuclear translocation of beta-catenin. Moreover, high glucose also activated the transcription and expression of matrix metallopeptidase and snail, which interfered with the adhesion of corneal epithelial cells to the basement membrane. These findings reveal that DK is associated with the dissociation of cell junctions. The maintenance of the stability of the beta-catenin/E-cadherin complex may be a potential therapeutic target of refractory corneal ulcers in patients with diabetes.