He Jia, Long Chongde, Huang Zixin, Zhou Xin, Kuang Xielan, Liu Lanying, Liu Huijun, Tang Yan, Fan Yuting, Ning Jie, Ma Xinqi, Zhang Qingjiong, Shen Huangxuan
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, China; Biobank of Eye, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, 54 Xianlie Road, Guangzhou 510060, China.
Biomed Res Int. 2017;2017:3681707. doi: 10.1155/2017/3681707. Epub 2017 Feb 22.
Age-related macular degeneration (AMD) is a leading cause of blindness and progressive loss of central vision in the elderly population. The important factor of AMD pathogenesis is the degeneration of retinal pigment epithelial (RPE) cells by oxidative stress. Inactivation of PTEN can disrupt intercellular adhesion in the RPE cells, but the mechanism of oxidative stress is less known. Here we presented evidence that UVB-mediated oxidative stress induced apoptosis in ARPE-19 cells. Downregulation of the expression of PTEN in UVB-irradiative RPE cells triggered DNA damage and increased the level of UVB-induced apoptosis by activating p53-dependent pathway. However, overexpression of PTEN increased cell survival by suppressing p-H2A in response to DNA damage and apoptosis. When using Pifithrin- (one of p53 inhibitors), the level of p53-dependent apoptosis was significantly lower than untreated, which suggested that p53 was possibly involved in PTEN-dependent apoptosis. Thus, it elucidated the molecular mechanisms of UVB-induced damage in RPE cells and may offer an alternative therapeutic target in dry AMD.
年龄相关性黄斑变性（AMD）是老年人失明和中心视力渐进性丧失的主要原因。AMD发病机制的重要因素是视网膜色素上皮（RPE）细胞因氧化应激而退化。PTEN的失活会破坏RPE细胞间的黏附，但氧化应激的机制尚不清楚。在此，我们提供证据表明紫外线B（UVB）介导的氧化应激可诱导ARPE-19细胞凋亡。UVB照射的RPE细胞中PTEN表达下调会引发DNA损伤，并通过激活p53依赖途径增加UVB诱导的凋亡水平。然而，PTEN的过表达通过抑制DNA损伤和凋亡反应中的p-H2A来提高细胞存活率。当使用p53抑制剂之一Pifithrin-α时，p53依赖的凋亡水平显著低于未处理组，这表明p53可能参与了PTEN依赖的凋亡。因此，它阐明了UVB诱导RPE细胞损伤的分子机制，并可能为干性AMD提供一个替代治疗靶点。
