Adult Human Müller Glia Cells Are a Highly Efficient Source of Rod Photoreceptors§

Authors

  • Serena G. Giannelli,

    1. Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
    2. Eye Repair Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
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  • Gian Carlo Demontis,

    1. Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy
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  • Grazia Pertile,

    1. Department of Ophthalmology, Ospedale Sacro Cuore, Negrar, Verona, Italy
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  • Paolo Rama,

    1. Eye Repair Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
    2. Ophthalmology Unit, San Raffaele Hospital, Milan, Italy
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  • Vania Broccoli

    Corresponding author
    1. Stem Cell and Neurogenesis Unit, Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy
    • San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy
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    • Telephone: 39-02-26434616; Fax 39-02-26434621


  • Author contributions: S.G.G.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, final approval of the manuscript; G.C.D.: conception and design, collection and assembly of data, final approval of manuscript; G.P.: provision of study material, final approval of manuscript; P.R.: conception and design, provision of study material, financial support, final approval of manuscript; V.B.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing, financial support, final approval of the manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS Month 00, 2010.

Abstract

There is growing evidence that Müller glia cells (MGCs) might act as regenerative elements in injured retinas of fishes and amniotes. However, their differentiation potential in humans is yet unknown. We isolated Müller glia from adult human retinas and propagated them in vitro revealing for the first time their ability to differentiate into rod photoreceptors. These results were also confirmed with mice retinas. Here, we describe conditions by which human MGCs adopt a rod photoreceptor commitment with a surprising efficiency as high as 54%. Functional characterization of Müller glia-derived photoreceptors by patch-clamp recordings revealed that their electrical properties are comparable to those of adult rods. Interestingly, our procedure allowed efficient derivation of MGC cultures starting from both injured and degenerating and postmortem human retinas. Human transplanted Müller glia-derived photoreceptors integrate and survive within immunodeficient mouse retinas. These data provide evidence that Müller glia retains an unpredicted plasticity and multipotent potential into adulthood, and it is therefore a promising source of novel therapeutic applications in retinal repair. STEM CELLS 2011;29:344–356

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