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Exosomes from Microglia Attenuate Photoreceptor Injury and Neovascularization in an Animal Model of Retinopathy of Prematurity.

Abstract：

:The role of microglia in the pathophysiology of ischemic retinal diseases has been studied extensively. Exosomes from microglial cells exert protective effects during several nervous system diseases, but their roles in hypoxia-induced retinopathy remain unclear. In our study, exosomes derived from microglial cells were injected into the vitreous body of mice with oxygen-induced retinopathy (OIR). Results showed that exosome-treated OIR mice exhibited smaller avascular areas and fewer neovascular tufts in addition to decreased vascular endothelial growth factor (VEGF) and transforming growth factor β (TGF-β) expression. Moreover, photoreceptor apoptosis was suppressed by exosome injection. Mechanistically, exosomes from microglial cells were incorporated into photoreceptors in vitro and inhibited the inositol-requiring enzyme 1α (IRE1α)-X-box binding protein 1 (XBP1) cascade, which contributes to hypoxia-induced photoreceptor apoptosis. Furthermore, the exosomes also downregulated the mRNA and protein levels of VEGF and TGF-β in hypoxia-exposed photoreceptors. A microRNA assay showed that microRNA-24-3p (miR-24-3p) levels were extremely high in exosomes from microglial cells, suggesting that this could be the key molecule that inhibits the hypoxia-induced expression of IRE1α in photoreceptors. These findings delineate a novel exosome-mediated mechanism of microglial cell-photoreceptor crosstalk that facilitates normal angiogenesis and visual function in OIR mice; thus, our results also suggest a potential therapeutic approach for retinopathy of prematurity.

journal_name

Mol Ther Nucleic Acids

journal_title

Molecular therapy. Nucleic acids

authors

Xu W,Wu Y,Hu Z,Sun L,Dou G,Zhang Z,Wang H,Guo C,Wang Y

doi

10.1016/j.omtn.2019.04.029

subject

Has Abstract

pub_date

2019-06-07 00:00:00

pages

778-790

issn

2162-2531

pii

S2162-2531(19)30124-6

journal_volume

16

pub_type

杂志文章

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