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Abstract #54574 Published in IGR 15-3

Atoh7 promotes the differentiation of retinal stem cells derived from Müller cells into retinal ganglion cells by inhibiting Notch signaling

Song WT; Zhang XY; Xia XB
Stem cell research & therapy 2013; 4: 94

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INTRODUCTION: Retinal Müller cells exhibit the characteristics of retinal progenitor cells, and differentiate into ganglion cells under certain conditions. However, the number of ganglion cells differentiated from retinal Müller cells falls far short of therapeutic needs. This study aimed to develop a novel protocol to promote the differentiation of retinal Müller cells into ganglion cells and explore the underlying signaling mechanisms. METHODS: Müller cells were isolated and purified from rat retina and induced to dedifferentiate into retinal stem cells. Next the stem cells were transfected with lentivirus PGC-FU-GFP or lentivirus PGC-FU-Atoh7-GFP. In addition, the stem cells were transfected with Brn-3b siRNA or Isl-1 siRNA or treated with Notch inhibitor gamma-secretase inhibitor (GSI). RESULTS: The proportion of ganglion cells differentiated from Atoh7-tranfected stem cells was significantly higher than that of controls. Knockdown of Brn-3b or Isl-1 inhibited, while GSI promoted, the differentiation into retinal ganglion cells. Atoh7 promoted the expression of Brn-3b and Isl-1 but inhibited the expression of Notch1. CONCLUSIONS: Atoh7 promotes the differentiation of Müller cells-derived retinal stem cells into retinal ganglion cells by inhibiting Notch signaling, thus opening up a new avenue for gene therapy and optic nerve regeneration in glaucoma.

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, China. xbxia21@163.com.

Full article

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Classification:

2.17 Stem cells (Part of: 2 Anatomical structures in glaucoma)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
11.9 Gene therapy (Part of: 11 Medical treatment)

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