Wang Liyin, Yu Xin, Zhang Dongyan, Wen Yingying, Zhang Liyue, Xia Yutong, Chen Jinbo, Xie Chen, Zhu Hong, Tong Jianping, Shen Ye
Department of Ophthalmology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 311003, China; Clinical Research Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 311003, China.
Department of Ophthalmology, Shaoxing Central Hospital, Shaoxing 312030, Zhejiang, China.
J Photochem Photobiol B. 2023 Mar;240:112654. doi: 10.1016/j.jphotobiol.2023.112654. Epub 2023 Jan 24.
Long-term light exposure, especially in the spectrum of blue light, frequently causes excessive oxidative stress in dry age-related macular degeneration (AMD). Here, to gain insight into the underlying mechanism, we focused on mitochondrial dynamics alterations under long-term exposure to blue light in mouse and retinal cells. Six-month-old C57BL/6 mice were exposed to blue light (450 nm, 800 lx) for 2 weeks. The phenotypic changes in the retina were assayed using haematoxylin-eosin staining and transmission electron microscopy. Long-term blue light exposure significantly thinned each retinal layer in mice, induced retinal apoptosis and impaired retinal mitochondria. A retinal pigment epithelial cell line (ARPE-19) was used to verify the phototoxicity of blue light. Flow cytometry, immunofluorescence and MitoSox Red probe experiments confirmed that more total and mitochondria-specific ROS were generated in the blue light group than in the control group. Mito-Tracker Green probe showed fragmented mitochondrial morphology. The western blotting results indicated a significant increase in DRP1, OMA1, and BAX and a decrease in OPA1 and Bcl-2. In conclusion, long-term exposure to blue light damaged the retinas of mice, especially the ONL and RPE cells. There was destruction and dysfunction of mitochondria in RPE cells in vivo and in vitro. Mitochondrial dynamics were disrupted with characteristics of fusion-related obstruction after blue-light irradiation.
长期光照,尤其是蓝光光谱范围内的光照,在干性年龄相关性黄斑变性(AMD)中常导致过度的氧化应激。在此,为深入了解其潜在机制,我们聚焦于小鼠和视网膜细胞长期暴露于蓝光下时线粒体动力学的改变。6月龄C57BL/6小鼠暴露于蓝光(450nm,800勒克斯)下2周。使用苏木精-伊红染色和透射电子显微镜检测视网膜的表型变化。长期蓝光暴露显著使小鼠视网膜各层变薄,诱导视网膜细胞凋亡并损害视网膜线粒体。使用视网膜色素上皮细胞系(ARPE-19)验证蓝光的光毒性。流式细胞术、免疫荧光和MitoSox Red探针实验证实,蓝光组比对照组产生了更多的总活性氧和线粒体特异性活性氧。Mito-Tracker Green探针显示线粒体形态碎片化。蛋白质印迹结果表明,动力相关蛋白1(DRP1)、OMA1和Bax显著增加,视神经萎缩蛋白1(OPA1)和Bcl-2减少。总之,长期蓝光暴露损害了小鼠视网膜,尤其是外核层(ONL)和视网膜色素上皮(RPE)细胞。体内和体外RPE细胞中线粒体均存在破坏和功能障碍。蓝光照射后线粒体动力学受到破坏,具有融合相关障碍的特征。