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Intravitreal injection of EV11, a novel aryl ketone amide, inhibits choroidal neovascularization via AKT/ERK1/2 pathway

文献类型：期刊论文

作者Kong, Hongyu2,3,4,5; Zhang, Rong2,3,4,5; Jing, Qinghe2,3,4,5; Liang, Yu2,3,4,5; Zhuo, Qiao2; Li, Bo1; Zhang, Shujie2,3,4,5; Zhu, Weiliang1; Zhao, Chen2,3,4,5
刊名MICROVASCULAR RESEARCH
出版日期2022-09-01
卷号143页码:7
ISSN号0026-2862
关键词Choroidal neovascularization Intravitreal injection AKT ERK1 2 pathway
DOI10.1016/j.mvr.2022.104401
通讯作者Zhang, Shujie(shujiezhang@fudan.edu.cn) ; Zhao, Chen(dr_zhaochen@fudan.edu.cn)
英文摘要Purpose: Choroidal neovascularization (CNV) is the major cause of irreversible vision loss associated with agerelated macular disease (AMD). The currently clinical chemical therapeutic strategies are of high cost and facing supply chain shortage. In our study, we aim to investigate EV11, a novel derivative from Sorafenib, as a new approach to inhibit the formation of CNV. Methods: Cell viability assay, wound healing assay, transwell assay and tube formation assay were applied to explore the effects of EV11 on human vascular endothelial cells (HUVECs). Western blotting analysis was performed to investigate the pathways when EV11 acts on HUVECs. Laser-induced CNV in mice and intravitreal injection of EV11 were applied to find out the efficacy of the drug in vivo. Histological examination and electroretinogram (ERG) evaluated the retinal morphology and visual function after drug application. Results: EV11 influenced the HUVECs cell viability as the concentration increasing after 24 hour incubation. It influenced HUVECs through suppressing AKT and ERK1/2 pathway. EV11 reduced CNV area with the optimal concentration of 200uM in mice eyes and compared with Bevacizumab, it had the same effect. The retinal thickness around the optic in each group was not influenced. The amplitudes of the a- and b-waves on scotopic and photopic ERG were not reduced after intravitreal injection. Conclusion: The present study indicated that EV11 affected the proliferation, migration and tube formation of HUVECs, inhibited the area of neovascular of laser induced choroidal neovascularization in mice eyes with no toxicity. EV11 could block the AKT/ERK1/2 signaling pathway in effects of HUVECs. This study unveiled a novel perspective drug EV11 to be a potential candidate for neovascularization.
WOS关键词MACULAR DEGENERATION ; SORAFENIB ; MODEL ; APOPTOSIS ; THERAPY
资助项目National Natural Science Foundation of China[82020108006] ; National Natural Science Foundation of China[81730025] ; National Natural Science Foundation of China[81670864] ; National Natural Science Foundation of China[81525006] ; Excellent Academic Leaders of Shanghai[18XD1401000] ; Open Research Funds of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University[303060202400375]
WOS研究方向Cardiovascular System & Cardiology
语种英语
出版者ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号WOS:000860723500003
源URL[http://119.78.100.183/handle/2S10ELR8/302655]  
专题中国科学院上海药物研究所
通讯作者Zhang, Shujie; Zhao, Chen
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res, Shanghai, Peoples R China
2.Shanghai Key Lab Visual Impairment & Restorat, 83 Fenyang Rd, Shanghai 200031, Peoples R China
3.Fudan Univ, Chinese Acad Med Sci, NHC Key Lab Myopia, Key Lab Myopia, 83 Fenyang Rd, Shanghai 200031, Peoples R China
4.Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, 83 Fenyang Rd, Shanghai 200031, Peoples R China
5.Fudan Univ, Eye Inst, 83 Fenyang Rd, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Kong, Hongyu,Zhang, Rong,Jing, Qinghe,et al. Intravitreal injection of EV11, a novel aryl ketone amide, inhibits choroidal neovascularization via AKT/ERK1/2 pathway[J]. MICROVASCULAR RESEARCH,2022,143:7.
APA Kong, Hongyu.,Zhang, Rong.,Jing, Qinghe.,Liang, Yu.,Zhuo, Qiao.,...&Zhao, Chen.(2022).Intravitreal injection of EV11, a novel aryl ketone amide, inhibits choroidal neovascularization via AKT/ERK1/2 pathway.MICROVASCULAR RESEARCH,143,7.
MLA Kong, Hongyu,et al."Intravitreal injection of EV11, a novel aryl ketone amide, inhibits choroidal neovascularization via AKT/ERK1/2 pathway".MICROVASCULAR RESEARCH 143(2022):7.

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来源：上海药物研究所

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