Wu Tsung-Tien, Chen Ying-Ying, Chang Hui-Yu, Kung Ya-Hsin, Tseng Ching-Jiunn, Cheng Pei-Wen
Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
Faculty of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
Antioxidants (Basel). 2020 Mar 25;9(4):273. doi: 10.3390/antiox9040273.
Cataracts are a major cause of visual acuity deterioration in diabetes mellitus (DM) in developed and developing countries. Studies have demonstrated that overproduction of AKR1B1 and receptor for advanced glycation end products (RAGE) plays a major role in the pathogenesis of diabetic cataracts, but it is unclear whether the prevalence of diabetic cataracts is related to epithelial-mesenchymal transition (EMT) in lens epithelial cells. This study aimed to analyze the role of EMT in cataract formation of DM patients.
Immunofluorescence and immunohistochemistry assays were used to estimate AKR1B1, RAGE, AMPK, and EMT levels in epithelial human lens of DM or non-DM cataracts.
Immunohistochemical staining demonstrated that pathologic phases and N-cadherin expression levels were significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Immunofluorescent staining showed that AKR1B1 and RAGE were significantly higher in epithelial human lens of DM (+) compared to DM (-) cataracts. Interestingly, acetyl superoxide dismutase 2 (AcSOD2) levels were significantly higher in DM patients' lens epithelial cells (LECs), whereas AMPKT172 phosphorylation was significantly increased in non-DM patients. This indicates that AMPKT172 might be related to superoxide reduction and diabetic cataract formation.
Our results suggest that AKR1B1 overexpression can decrease AMPK activation, thereby increasing AcSOD2 and RAGE-induced EMT in epithelial human lens of DM cataracts. These novel findings suggest that AKR inhibitors may be candidates for the pharmacological prevention of cataracts in patients with DM.
在发达国家和发展中国家，白内障是糖尿病（DM）患者视力下降的主要原因。研究表明，醛糖还原酶1B1（AKR1B1）和晚期糖基化终末产物受体（RAGE）的过度产生在糖尿病性白内障的发病机制中起主要作用，但尚不清楚糖尿病性白内障的患病率是否与晶状体上皮细胞的上皮-间质转化（EMT）有关。本研究旨在分析EMT在糖尿病患者白内障形成中的作用。
采用免疫荧光和免疫组化分析方法评估糖尿病性或非糖尿病性白内障患者人晶状体上皮中AKR1B1、RAGE、AMPK和EMT的水平。
免疫组化染色显示，与糖尿病（-）白内障相比，糖尿病（+）患者人晶状体上皮的病理分期和N-钙黏蛋白表达水平显著更高。免疫荧光染色显示，与糖尿病（-）白内障相比，糖尿病（+）患者人晶状体上皮中AKR1B1和RAGE显著更高。有趣的是，糖尿病患者晶状体上皮细胞（LECs）中的乙酰超氧化物歧化酶2（AcSOD2）水平显著更高，而非糖尿病患者中AMPK T172磷酸化显著增加。这表明AMPK T172可能与超氧化物还原和糖尿病性白内障形成有关。
我们的结果表明，AKR1B1的过表达可降低AMPK的激活，从而增加糖尿病性白内障患者人晶状体上皮中AcSOD2和RAGE诱导的EMT。这些新发现表明，AKR抑制剂可能是糖尿病患者白内障药物预防的候选药物。
