D609 protects retinal pigmented epithelium as a potential therapy for age-related macular degeneration  

作　　者：Bowen Wang Li Wang Sijie Gu Yankun Yu Huaxing Huang Kunlun Mo He Xu Fanzhu Zeng Yichen Xiao Lulu Peng Chunqiao Liu Nan Cao Yizhi Liu Jin Yuan Hong Ouyang 

机构地区：[1]State Key Laboratory of Ophthalmology,Zhongshan Ophthalmic Center,Sun Yat-sen University,Guangzhou 510623,China [2]Program of Stem Cells and Regenerative Medicine,Fifth Affiliated Hospital,Zhongshan School of Medicine,Sun Yat-Sen University,Guangdong 510080,China

出　　处：《Signal Transduction and Targeted Therapy》2020年第1期2280-2291,共12页信号转导与靶向治疗（英文）

基　　金：The National Key Research and Development(R&D)Program of China(2016YFA0101700);National Natural Science Foundation of China(81700805,81622012 and 81870633);Fundamental Research Funds for the Central Universities(17ykjc28);Fundamental Research Funds of the State Key Laboratory of Ophthalmology.Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S029).

摘　　要：Accumulated oxidative damage may lead to irreversible retinal pigmented epithelium(RPE)cell death,which is considered to be the primary cause of dry age-related macular degeneration(AMD),leading to blindness in the elderly.However,an effective therapy for this disease is lacking.Here,we described a robust high-content screening procedure with a library of 814 protective compounds and found that D609 strongly protected RPE cells from sodium iodate(SI)-induced oxidative cell death and prolonged their healthy survival.D609 effectively attenuated excessive reactive oxygen species(ROS)and prevented severe mitochondrial loss due to oxidative stress in the RPE cells.Surprisingly,the potent antioxidative effects of D609 were not achieved through its own reducibility but were primarily dependent on its ability to increase the expression of metallothionein.The injection of this small water-soluble molecule also showed an explicit protective effect of the RPE layer in an SI-induced AMD mouse model.These findings suggested that D609 could serve as a novel antioxidative protector of RPE cells both in vitro and in vivo and unveiled a novel antioxidative mechanism of D609,which may ultimately have clinical applications for the treatment of AMD.

关 键 词：D609 DEGENERATION protective 

分 类 号：R774.5[医药卫生—眼科]