Chen Mengmeng, Fu Yushan, Wang Xu, Wu Ruitong, Su Dongmei, Zhou Nan, Qi Yanhua
Department of Ophthalmology, The Second Affiliated Hospital of Harbin Medical University, 150001, Harbin, China.
Department of Ophthalmology, Xixi Hospital of Hangzhou, 310023, Hangzhou, China.
Cell Death Discov. 2022 Jan 10;8(1):8. doi: 10.1038/s41420-021-00800-w.
The senescence of lens epithelial cells (LECs) is a major factor leading to age-related cataract (ARC). ARC results in visual impairment and severe vision loss in elderly patients. However, the specific mechanism of ARC remains unclear, and there are no effective therapeutic agents to halt the formation of ARC. This study aimed to assess the underlying mechanism of the formation of ARC and investigate the potential anti-ageing effect of metformin (MET) on ARC. Male C57BL/6 mice were divided into three groups: the control group having young mice (3 months old, n = 40), the naturally aged group (aged 20 months, n = 60) and the MET group (MET, 20 months, n = 60). Mice in the control and the naturally aged groups were fed a standard purified mouse diet ad libitum and water, whereas those in the MET group were fed chows supplemented with 0.1% MET for 10 months. The transparency of the lens and age-associated proteins p21 and p53 were analysed in the LECs of these three groups. Furthermore, we determined the expressions of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway and the effect of MET on this pathway in LECs during the ageing process of ARC. In addition, the relationship between autophagy and the senescence of LECs and the role of MET in the autophagy of LECs during the ageing process of ARC were examined. Our results indicated that age-related inactivation of the AMPK pathway and impairment of autophagy might contribute to the senescence of LECs and the occurrence of ARC. More importantly, these results demonstrated that MET effectively alleviated the senescence of LECs and the formation of ARC probably via inactivation of the AMPK pathway and augmentation of autophagy. These findings revealed that MET can be exploited as a potentially useful drug for ARC prevention. Our study will help in enlightening the development of innovative strategies for the clinical treatment of ARC.
晶状体上皮细胞（LECs）的衰老 是导致年龄相关性白内障（ARC）的主要因素。ARC会导致老年患者视力受损和严重视力丧失。然而，ARC的具体机制仍不清楚，并且没有有效的治疗药物来阻止ARC的形成。本研究旨在评估ARC形成的潜在机制，并研究二甲双胍（MET）对ARC的潜在抗衰老作用。将雄性C57BL/6小鼠分为三组：对照组为年轻小鼠（3个月大，n = 40），自然衰老组（20个月大，n = 60）和MET组（MET，20个月大，n = 60）。对照组和自然衰老组的小鼠随意喂食标准纯化的小鼠饮食和水，而MET组的小鼠喂食添加有0.1% MET的食物10个月。分析了这三组LECs中晶状体的透明度以及与年龄相关的蛋白质p21和p53。此外，我们确定了腺苷单磷酸（AMP）激活的蛋白激酶（AMPK）途径的表达以及MET在ARC衰老过程中对LECs中该途径的影响。此外，还研究了自噬与LECs衰老之间的关系以及MET在ARC衰老过程中对LECs自噬的作用。我们的结果表明，与年龄相关的AMPK途径失活和自噬受损可能导致LECs衰老和ARC的发生。更重要的是，这些结果表明MET可能通过使AMPK途径失活和增强自噬来有效减轻LECs衰老和ARC的形成。这些发现表明，MET可被开发为一种潜在的预防ARC的有用药物。我们的研究将有助于启发ARC临床治疗创新策略的发展。
