Neural Regeneration Research ›› 2023, Vol. 18 ›› Issue (10): 2315-2320.doi: 10.4103/1673-5374.369123

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

Tian-Qi Duan1, Zhao-Lin Gao1, Ai-Xiang Luo1, Dan Chen1, Jian-Bin Tong2, Ju-Fang Huang1, *   

  1. 1Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan Province, China; 2Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, Hunan Province, China
  • Online:2023-10-15 Published:2023-03-29
  • Contact: Ju-Fang Huang, PhD, huangjufang@csu.edu.cn.
  • Supported by:
    This study was 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 Hunan Province, No. 2021JJ30891 (to DC); the Human Resource Bank Program of Hunan Province, No. 2020TP3003 (to JFH); and the School-Enterprise Joint Program of Central South University, No. 2021XQLH092 (to TQD).

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Abstract: 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 of α-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 ADSC-EVs ameliorate glutamate-induced excitotoxicity in the retina through inhibiting protein kinase C alpha activation. 

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