Open AccessOtx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells
Author(s) -
Xiong Yu,
Ji Hongpei,
You Zhipeng,
Yao Fei,
Zhou Rongrong,
Song Weitao,
Xia Xiaobo
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13995
Subject(s) - transdifferentiation , retinal , retinal degeneration , microbiology and biotechnology , retinal regeneration , wnt signaling pathway , retina , stem cell , biology , progenitor cell , photoreceptor cell , muller glia , chemistry , signal transduction , neuroscience , biochemistry
Retinal Müller glial cells have the potential of neurogenic retinal progenitor cells, and could reprogram into retinal‐specific cell types such as photoreceptor cells. How to promote the differentiation of Müller cells into photoreceptor cells represents a promising therapy strategy for retinal degeneration diseases. This study aimed to enhance the transdifferentiation of rat Müller cells‐derived retinal stem cells ( MC ‐ RSC s) into photoreceptor‐like cells and explore the signalling mechanism. We dedifferentiated rat Müller cells into MC ‐ RSC s which were infected with Otx2 overexpression lentivirus or control. The positive rate of photoreceptor‐like cells among MC ‐ RSC s treated with Otx2 overexpression lentivirus was significantly higher compared to control. Furthermore, pre‐treatment with Crx si RNA , Nrl si RNA , or GSK ‐3 inhibitor SB ‐216763 reduced the positive rate of photoreceptor‐like cells among MC ‐ RSC s treated with Otx2 overexpression lentivirus. Finally, Otx2 induced photoreceptor precursor cells were injected into subretinal space of N ‐methyl‐ N ‐nitrosourea induced rat model of retinal degeneration and partially recovered retinal degeneration in the rats. In conclusion, Otx2 enhances transdifferentiation of MC ‐ RSC s into photoreceptor‐like cells and this is associated with the inhibition of Wnt signalling. Otx2 is a potential target for gene therapy of retinal degenerative diseases.