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

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.