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Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas.
Yao, Kai; Qiu, Suo; Wang, Yanbin V; Park, Silvia J H; Mohns, Ethan J; Mehta, Bhupesh; Liu, Xinran; Chang, Bo; Zenisek, David; Crair, Michael C; Demb, Jonathan B; Chen, Bo.
Afiliación
  • Yao K; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Qiu S; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Wang YV; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
  • Park SJH; Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA.
  • Mohns EJ; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
  • Mehta B; Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA.
  • Liu X; Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
  • Chang B; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
  • Zenisek D; Department of Biophysics, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
  • Crair MC; Department of Cell Biology, Center for Cellular and Molecular Imaging, Yale University School of Medicine, New Haven, CT, USA.
  • Demb JB; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Chen B; Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA.
Nature ; 560(7719): 484-488, 2018 08.
Article en En | MEDLINE | ID: mdl-30111842
In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision1. In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis2-7. Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of ß-catenin stimulates MG proliferation in the absence of injury in mouse retinas8. Here we report that following gene transfer of ß-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1rd17Gnat2cpfl3 double mutant mice, a model of congenital blindness9,10, throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Células Fotorreceptoras Retinianas Bastones / Reprogramación Celular / Neurogénesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Células Fotorreceptoras Retinianas Bastones / Reprogramación Celular / Neurogénesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Nature Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido