Wu Tsung-Tien, Chen Ying-Ying, Ho Chiu-Yi, Yeh Tung-Chen, Sun Gwo-Ching, Tseng Ching-Jiunn, Cheng Pei-Wen
Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Antioxidants (Basel). 2021 Jul 6;10(7):1086. doi: 10.3390/antiox10071086.
Studies demonstrated that the receptor of advanced glycation end products (RAGE) induced epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells (LECs) of diabetic cataracts. This work investigated how 3H-1,2-dithiole-3-thione (D3T) reduces EMT formation in LECs of the fructose-induced diabetes mellitus (DM). LECs were isolated during cataract surgery from patients without DM or with DM. In a rat model, fructose (10% fructose, eight weeks) with or without D3T (10 mg/kg/day) treatment induced DM, as verified by blood pressure and serum parameter measurements. We observed that the formation of advanced glycation end products (AGEs) was significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Aldose reductase (AKR1B1), AcSOD2, and 3-NT were significantly enhanced in the rat lens epithelial sections of fructose-induced DM, however, the phosphorylation level of AMPK showed a reversed result. Interestingly, administration of D3T reverses the fructose-induced effects in LECs. These results indicated that AMPK may be required for reduced superoxide generation and the pathogenesis of diabetic cataract. Administration of D3T reverses the fructose-induced EMT formation the LECs of fructose-induced DM. These novel findings suggest that the D3T may be a candidate for the pharmacological prevention of cataracts in patients with DM.
研究表明，晚期糖基化终末产物受体（RAGE）可诱导糖尿病性白内障晶状体上皮细胞（LECs）发生上皮-间质转化（EMT）。本研究探讨了3H-1,2-二硫杂环戊烯-3-硫酮（D3T）如何减少果糖诱导的糖尿病（DM）模型中LECs的EMT形成。在白内障手术期间从无DM或患有DM的患者中分离出LECs。在大鼠模型中，通过血压和血清参数测量验证，给予果糖（10%果糖，8周），无论有无D3T（10mg/kg/天）处理均可诱导DM。我们观察到，与DM（-）白内障相比，DM（+）人晶状体上皮中晚期糖基化终末产物（AGEs）的形成显著更高。在果糖诱导的DM大鼠晶状体上皮切片中，醛糖还原酶（AKR1B1）、乙酰超氧化物歧化酶2（AcSOD2）和3-硝基酪氨酸（3-NT）显著增强，然而，AMPK的磷酸化水平呈现相反的结果。有趣的是，给予D3T可逆转果糖对LECs的诱导作用。这些结果表明，AMPK可能是减少超氧化物生成和糖尿病性白内障发病机制所必需的。给予D3T可逆转果糖诱导的DM大鼠LECs中的EMT形成。这些新发现表明，D3T可能是DM患者白内障药物预防的候选药物。
