Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
Department of Neurosurgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen 529030, China.
Exp Biol Med (Maywood). 2021 May;246(10):1167-1176. doi: 10.1177/1535370220983243. Epub 2021 Feb 7.
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 β-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 β-catenin increased in nuclear. High glucose-induced degradation and endocytosis of E-cadherin of corneal epithelial cells reduce the formation of β-catenin/E-cadherin complex and promote the nuclear translocation of β-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 β-catenin/E-cadherin complex may be a potential therapeutic target of refractory corneal ulcers in patients with diabetes.
复发性上皮糜烂和难治性角膜溃疡是糖尿病角膜病变（DK）的临床特征，最终导致角膜瘢痕和视力障碍。在本研究中，我们试图确定糖尿病角膜上皮细胞细胞连接的异常以及高葡萄糖对β-连环蛋白/E-钙黏蛋白复合物的影响。角膜组织学显示，高糖组小鼠的角膜上皮细胞排列松散，免疫组织化学显示 E-钙黏蛋白表达减少，β-连环蛋白在核内增加。高葡萄糖诱导的角膜上皮细胞 E-钙黏蛋白的降解和内吞作用减少了β-连环蛋白/E-钙黏蛋白复合物的形成，并促进了β-连环蛋白的核转位。此外，高葡萄糖还激活了基质金属蛋白酶和蜗牛的转录和表达，干扰了角膜上皮细胞与基底膜的黏附。这些发现表明 DK 与细胞连接的解离有关。维持β-连环蛋白/E-钙黏蛋白复合物的稳定性可能是糖尿病患者难治性角膜溃疡的潜在治疗靶点。
