MiR-124 Promotes the Growth of Retinal Ganglion Cells Derived from Muller Cells
MiR-124 Promotes the Growth of Retinal Ganglion Cells Derived from Muller Cells
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MiR-124 促进源自 Muller 细胞的视网膜神经节细胞的生长
DOI：
10.1159/000487292
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Song, Wei-tao
中科院分区：
文献类型：
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作者：
He, Ye;Li, Hai-bo;Song, Wei-tao
背景/目标：视网膜Muller细胞可被诱导分化为视网膜神经节细胞（retinal ganglion cells，RGCs），但Muller细胞来源的RGCs轴突生长缺陷，导致信号传导缺陷。本研究旨在探讨miR-124在Muller细胞来源的RGCs轴突生长中的作用。方法：分离大鼠视网膜Muller细胞，诱导其去分化为视网膜干细胞。用PGC-FU-Atoh 7-GFP慢病毒感染干细胞，然后用miR-124或anti-miR-124转染，比较轴突长度。并将其注射到慢性高眼压性青光眼大鼠模型眼内，观察其轴突生长情况。荧光素酶法检测miR-124对CoREST的靶向性。结果如下：在视网膜干细胞中，miR-124组的轴突长度为1，792 +/- 64.54 μ m，对照组为509 +/- 21.35 μ m，而anti-miR-124组仅为87.9 +/- 9.24 μ m。在大鼠模型中，miR-124促进从视网膜干细胞分化的RGCs的轴突生长。此外，我们发现miR-124通过直接靶向CoREST 3' UTR中的结合位点来负调控CoREST。结论：我们首次证明miR-124调节Muller细胞来源的RGCs轴突生长，miR-124具有转译青光眼基因治疗的潜力。(C)2018作者（S）由S发布。Karger AG，巴塞尔
Background/Aims: Retinal Muller cells could be induced to differentiate into retinal ganglion cells (RGCs), but RGCs derived from Muller cells have defects in axon growth, leading to a defect in signal conduction. In this study we aimed to explore the role of miR-124 in axon growth of RGCs derived from Muller cells. Methods: Muller cells were isolated from rat retina and induced to dedifferentiate into retinal stem cells. The stem cells were infected by PGC-FU-Atoh7-GFP lentivirus and then transfected with miR-124 or anti-miR-124, and the length of axon was compared. Furthermore, the cells were injected into the eyes of rat chronic ocular hypertension glaucoma model and axon growth in vivo was examined. The targeting of CoREST by miR-124 was detected by luciferase assay. Results: In retinal stem cells, the length of axon was 1,792 +/- 64.54 mu m in miR-124 group, 509 +/- 21.35 mu m in control group, and only 87.9 +/- 9.24 mu m in anti-miR-124 group. In rat model, miR-124 promoted axon growth of RGCs differentiated from retinal stem cells. Furthermore, we found that miR-124 negatively regulated CoREST via directly targeting the binding site in CoREST 3' UTR. Conclusions: We provide the first evidence that miR-124 regulates axon growth of RGCs derived from Muller cells, and miR-124 has translational potential for gene therapy of glaucoma. (C) 2018 The Author(s) Published by S. Karger AG, Basel