Adipose mesenchymal stem cell-derived extracellular vesicles reduce glutamate-induced excitotoxicity in the retina

作     者：Tian-Qi Duan Zhao-Lin Gao Ai-Xiang Luo Dan Chen Jian-Bin Tong Ju-Fang Huang Tian-Qi Duan;Zhao-Lin Gao;Ai-Xiang Luo;Dan Chen;Jian-Bin Tong;Ju-Fang Huang

作者机构：Department of Anatomy and NeurobiologySchool of Basic Medical SciencesCentral South UniversityChangshaHunan ProvinceChina Hunan Province Key Laboratory of Brain HomeostasisThird Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第10期

页      面：2315-2320页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100212[医学-眼科学] 10[医学] 

基　　金：supported by the National Key R&D Program of China,No.2016YFC1201800(to JFH) the Key Research and Development Program of Hunan Province,Nos.2018SK2090(to JFH),2022SK2079(to JFH) the Natural Science Foundation of Hu nan Province,No.2021JJ30891(to DC) the Human Resource Bank Program of Hunan Province,No.2020TP3003(to JFH) the School-Enterprise Joint Program of Central South University,No.2021XQLH092(to TQD)。 

主　　题：adipose mesenchymal stem cells calcium overload electroretinography excitotoxicity extracellular vesicles GluA2 glutamate protein kinase C alpha R28 cells retina retinal ganglion cell 

摘      要：Adipose mesenchymal stem cells(ADSCs)have protective effects against glutamate-induced excitotoxicity,but ADSCs are limited in use for treatment of optic nerve injury.Studies have shown that the extracellular vesicles(EVs)secreted by ADSCs(ADSC-EVs)not only have the function of ADSCs,but also have unique advantages including non-immunogenicity,low probability of abnormal growth,and easy access to target cells.In the present study,we showed that intravitreal injection of ADSC-EVs substantially reduced glutamate-induced damage to retinal morphology and electroretinography.In addition,R28 cell pretreatment with ADSC-EVs before injury inhibited glutamate-induced overload of intracellular calcium,downregulation ofα-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor(AMPAR)subunit GluA2,and phosphorylation of GluA2 and protein kinase C alpha in vitro.A protein kinase C alpha agonist,12-O-tetradecanoylphorbol 13-acetate,inhibited the neuroprotective effects of ADSC-EVs on glutamate-induced R28 cells.These findings suggest that ADSCEVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation.