Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma
Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma
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DOI：
10.1177/1535370214560965
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发表时间：
2015-02
影响因子：
3.2
通讯作者：
Wei‐tao Song;Xue-yong Zhang;X. Xia
中科院分区：
文献类型：
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作者：
Wei‐tao Song;Xue-yong Zhang;X. Xia
青光眼是由于视网膜神经节细胞死亡而导致失明的主要眼病之一。本研究的目的是在青光眼大鼠模型中建立一种新的方法来促进视网膜网膜下丘脑细胞向神经节细胞的分化。将去分化的大鼠视网膜上皮细胞干细胞随机分为转染空慢病毒PGC-FU-GFP、慢病毒PGC-FU-Atoh7-GFP和不转染。进一步诱导干细胞分化。采用激光光凝术诱导高眼压。眼内注射Atoh7表达载体慢病毒PGC-FU-Atoh7-GFP。眼球冷冻切片、免疫组化、RT-PCR、Western bolt、细胞凋亡检测。我们发现转染atoh7的干细胞分化成神经节细胞的比例明显高于其他两组。青光眼眼的平均眼压明显高于对侧眼。慢性高眼压性青光眼模型大鼠视网膜内核层部分胞浆细胞进入有丝分裂细胞周期。Atoh7参与青光眼模型大鼠视网膜束细胞向视网膜神经节细胞的分化。综上所述，Atoh7在青光眼大鼠模型中促进m<s:1> ller细胞来源的视网膜干细胞向视网膜神经节细胞的分化，从而为青光眼的基因治疗和视神经再生开辟了新的途径。
Glaucoma is one of the leading eye diseases resulting in blindness due to the death of retinal ganglion cells. This study aimed to develop novel protocol to promote the differentiation of retinal Müller cells into ganglion cells in vivo in a rat model of glaucoma. The stem cells dedifferentiated from rat retinal Müller cells were randomized to receive transfection with empty lentivirus PGC-FU-GFP or lentivirus PGC-FU-Atoh7-GFP, or no transfection. The stem cells were induced further to differentiate. Ocular hypertension was induced using laser photocoagulation. The eyes were injected with Atoh7 expression vector lentivirus PGC-FU-Atoh7-GFP. Eyeball frozen sections, immunohistochemistry, RT-PCR, Western bolt, and apoptosis assay were performed. We found that the proportion of ganglion cells differentiated from Atoh7-tranfected stem cells was significantly higher than that of the other two groups. The mean intraocular pressure of glaucomatous eyes was elevated significantly compared with those of contralateral eyes. Some retinal Müller cells in the inner nuclear layer entered the mitotic cell cycle in rat chronic ocular hypertension glaucoma model. Atoh7 contributes to the differentiation of retinal Müller cells into retinal ganglion cells in rat model of glaucoma. In conclusion, Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells in a rat model of glaucoma, thus opening up a new avenue for gene therapy and optic nerve regeneration in glaucoma.