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 

机构地区：[1]Department of Anatomy and Neurobiology,School of Basic Medical Sciences,Central South University,Changsha,Hunan Province,China [2]Hunan Province Key Laboratory of Brain Homeostasis,Third Xiangya Hospital,Central South University,Changsha,Hunan Province,China

出　　处：《Neural Regeneration Research》2023年第10期2315-2320,共6页中国神经再生研究（英文版）

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)。

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.

关 键 词：adipose mesenchymal stem cells calcium overload ELECTRORETINOGRAPHY EXCITOTOXICITY extracellular vesicles GluA2 GLUTAMATE protein kinase C alpha R28 cells RETINA retinal ganglion cell 

分 类 号：R774.1[医药卫生—眼科]