Otx2 enhances transdifferentiation of Müller cells‐derived retinal stem cells into photoreceptor‐like cells. Issue 2 (19th November 2018)

• Record Type: Journal Article
• Authors: Xiong, Yu; Ji, Hongpei; You, Zhipeng; Yao, Fei; Zhou, Rongrong; Song, Weitao; Xia, Xiaobo
• Is Part Of: Journal of cellular and molecular medicine. Volume 23:Issue 2(2019)
• Page Start: 943
• Page End: 953
• Publication Date: 2018-11-19
• Subjects: Müller cells -- Otx2 -- photoreceptor cells -- stem cells -- Wnt signalling; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.13995
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: 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‐RSCs) into photoreceptor‐like cells and explore the signalling mechanism. We dedifferentiated rat Müller cells into MC‐RSCs which were infected with Otx2 overexpression lentivirus or control. The positive rate of photoreceptor‐like cells among MC‐RSCs treated with Otx2 overexpression lentivirus was significantly higher compared to control. Furthermore, pre‐treatment with Crx siRNA, Nrl siRNA, or GSK‐3 inhibitor SB‐216763 reduced the positive rate of photoreceptor‐like cells among MC‐RSCs 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‐RSCs 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.