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F. Gao, Z. Qu, Y. Guan, L. Cui, Y. Wu, W. Li, G.-T. Xu; Improvement of Sodium Iodate-Induced Retinal Degeneration in Mouse by Subretinal Transplantation of iPSCs-Derived NPCs. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3150.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the transplantation potential of neural precursor cells (NPCs) that are derived from C57 mouse induced pluripotent stem cells (iPSCs) under the subretinal space in retinal degeneration mouse model induced by Sodium Iodate (SI).
A C57 mouse iPSC line was generated by ectopic expression of the four define transcription factors Oct4, Sox2, Klf4 and cMyc in the mouse embryonic fibroblasts. The mouse iPSCs were characterized by RT-PCR, immunofluorescence and differentiation assays in vitro. Mouse iPSCs were induced to differentiate into NPCs by the embryoid body (EB) formation method. The differentiated NPCs were transplanted into subretinal space of SI-induced mouse which had been evaluated by electroretinogram (ERG), histology (HE staining) and immunohistology (TUNEL assay). The therapeutic effects of NPCs’ transplantation were monitored by ERG and fundus examination. The abilities of NPCs in terms of survival, integration and differentiation into retinal cells after subretinal transplantation were also examined by histology and immunohistology.
Mouse iPSCs exhibited similarity to mouse embryonic stem cells (mESCs) in morphology and expression profile of characteristic pluripotency markers. The mouse iPSCs were successfully differentiated into derivatives of all three embryonic germ layers in vitro. Highly enriched cultures of NPCs expressing transcripts of key regulatory genes of retinal development were developed from the iPSCs. The SI-induced retinal degeneration showed a time dependent severity. After transplantation into mouse eyes, the NPCs survived, migrated and integrated into the host retina. Furthermore, these transplanted NPCs can improve the retinal function of SI-induced retinal degeneration.
The iPSCs, which are similar to ESCs, could be efficiently induced to differentiate into NPCs. The subretinal transplantation of NPCs appears to improve the function of degenerative retina induced by SI in mouse. These findings indicate that iPSCs can be used for therapeutic applications in retinal degenerations.
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