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MicroRNA-24 protects retina from degeneration in rats by down-regulating chitinase-3-like protein 1
Journal article   Peer reviewed

MicroRNA-24 protects retina from degeneration in rats by down-regulating chitinase-3-like protein 1

Chunpin Lian, Hui Lou, Jingfa Zhang, Haibin Tian, Qingjian Ou, Jing-Ying Xu, Caixia Jin, Furong Gao, Jieping Zhang, Juan Wang, …
Experimental eye research, v 188, 107791
Nov 2019
DOI: https://doi.org/10.1016/j.exer.2019.107791
PMID: 31491426
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Autophagy Chitinase-3-like protein 1 MicroRNA-24 Retinal degeneration RPE
MicroRNAs (miRNAs) have been shown to play critical roles in the pathogenesis and progression of degenerative retinal diseases like age-related macular degeneration (AMD). In this study, we first demonstrated that miR-24 plays an important role in maintaining retinal structure and visual function of rats by targeting chitinase-3-like protein 1 (CHI3L1). In the retinal pigment epithelial (RPE) cells of Royal College of Surgeons (RCS) rats, an animal model of genetic retinal degeneration (RD), miR-24 was found lower and CHI3L1 level was higher in comparison with those in Sprague-Dawley (SD) rats. Other changes in the eyes of RCS rats include activated AKT/mTOR and ERK pathways and abnormal autophagy in the RPE cells. Such roles of miR-24 and CHI3L1 were further confirmed in RCS rats by subretinal injection of agomiR-24, which decreased CHI3L1 level and preserved retinal structure and function. Upstream, NF-κB was identified as the regulator of miR-24 in the RPE cells of these rats. On the other hand, in SD rats, intraocular treatment of antagomiR-24 induced pathological changes similar to those in RCS rats. The results revealed the protective roles for miR-24 to RPE cells and a mechanism for RD in RCS rats was proposed: extracellular stress stimuli first activate the NF-κB signaling pathway, which lowers miR-24 expression so that CHI3L1 increased. CHI3L1 sequentially results in aberrant autophagy and RPE dysfunction by activating AKT/mTOR and ERK pathways. Taken together, although the possibility, that the therapeutic effects in RCS rats are caused by other transcriptional changes regulated by miR-24, cannot be excluded, these findings indicate that miR-24 protects rat retina by targeting CHI3L1. Thus, miR-24 and CHI3L1 might be the targets for developing more effective therapy for degenerative retinal diseases like AMD. •miR-24 plays an important role in maintaining the visual function of rats.•Chitinase-3-like protein 1 (CHI3L1) was identified as the target of miR-24 in rats.•A mechanism for miR-24 in inducing retinal degeneration in RCS rats is proposed.•The mechanism involves regulating inflammation and autophagy by repressing CHI3L1.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Ophthalmology
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