Exosomes derived from MSCs ameliorate retinal laser injury partially by inhibition of MCP-1.

Bo Yu,Qiutang Li,Xiaomin Zhang,Yuanfeng Jiang,Yan Zhang,Lingling Bai,Chang Su,Xiaorong Li,Hui Shao,Xiteng Chen

doi:10.1038/srep34562

Abstract

Although accumulated evidence supports the notion that mesenchymal stem cells (MSCs) act in a paracrine manner, the mechanisms are still not fully understood. Recently, MSC-derived exosomes (MSC-Exos), a type of microvesicle released from MSCs, were thought to carry functional proteins and RNAs to recipient cells and play therapeutic roles. In the present study, we intravitreally injected MSCs derived from either mouse adipose tissue or human umbilical cord, and their exosomes to observe and compare their functions in a mouse model of laser-induced retinal injury. We found that both MSCs and their exosomes reduced damage, inhibited apoptosis, and suppressed inflammatory responses to obtain better visual function to nearly the same extent in vivo. Obvious down-regulation of monocyte chemotactic protein (MCP)-1 in the retina was found after MSC-Exos injection. In vitro, MSC-Exos also down-regulated MCP-1 mRNA expression in primarily cultured retinal cells after thermal injury. It was further demonstrated that intravitreal injection of an MCP-1-neutralizing antibody promoted the recovery of retinal laser injury, whereas the therapeutic effect of exosomes was abolished when MSC-Exos and MCP-1 were administrated simultaneously. Collectively, these results suggest that MSC-Exos ameliorate laser-induced retinal injury partially through down-regulation of MCP-1.

Highlights

Further experiments revealed that blocking monocyte chemotactic protein (MCP)-1 ameliorated retinal injury, whereas injection of MCP-1 abolished the protective effect of MSC-Exos, suggesting that MSC-Exos reduce retinal impairment partially by targeting MCP-1
Our results demonstrate that suppression of MCP-1 induction during laser induced retina injury reduces retina tissue damage, suggesting that MSC-Exos may afford the tissue protection activity partially through MCP-1 inhibition
MSC therapy is currently being translated into clinical application to a variety of diseases, and the mechanisms underlying their therapeutic effects are mainly attributed to a paracrine pattern

Summary

Introduction

Except for day 1, maMSC- and maMSC-Exo-treated eyes showed equivalent amelioration with milder disorganization of the tissue, more residual photoreceptor cells, less inflammatory cell infiltration, smaller retinal disordered areas, and ONL defect areas compared with the control group (Fig. 2C), suggesting that the therapeutic efficacy of maMSC-Exos is equal with that of maMSCs. In addition to the histology examination, we detected the improvement of dark- and light-adapted electroretinogram (ERG) responses in laser-injured mice treated with maMSCs or maMSC-Exos to evaluate retinal function. (D1) Amplitudes of dark-adapted ERG at 3, 14 and 60 days post-injury of PBS, maMSC- or maMSC-Exo-treated group.

Results

Conclusion