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G.A. Limb, J.M. Lawrence, T.A. Reh, P.T. Khaw; Localization of Müller Glia With Neural Stem Cell Characteristics in the Adult Human Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3231.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify the localization of Müller glia with stem cell characteristics in the adult human neural retina and to determine the pluripotent ability of these cells to de–differentiate in vitro as a true stem cell population. Methods: Frozen sections of cadaveric donor retinae from 4 donors 50–83 years old, consented for research and obtained from Moorfield’s Eye Hospital Eye Bank, were analysed by confocal microscopy for co–expression of the Müller cell markers CRALBP or nestin, and markers of progenitor cells of the embryonic neuroepithelium and developing retina, including Sox–2, Chx10, Pax–6 and Shh. Müller cells were also isolated from the neural retina after removal of the ciliary body and clones derived from single cells were examined for expression of progenitor markers, self–renewal and pluripotent abilities. Results: Examination of the neural retina up to a distance of 2–2.5 cm from the ciliary body showed that a population of cells with characteristic Müller cell morphology that expressed CRALBP or nestin, also expressed the neural progenitor markers Sox–2, Chx10 and Pax–6, as well as Shh, a marker of ganglion cells in the developing retina. The frequency of Müller cells co–expressing these markers was higher in the peripheral retina (2–5% of cells in the INL) than in the central retina (1–2% of cells in the INL). Müller cells expressing progenitor markers were spontaneously immortalized in vitro and displayed true multipotent stem cell characteristics as demonstrated by their self–renewal ability and their capacity to de–differentiate into neurospheres and to generate different types of retinal neurons. Conclusions: We showed that a population of Müller cells from the adult human retina that exhibit markers of neural stem cells and retinal progenitors in situ, are found widespread distributed throughout the neural retina. These cells can be easily characterized and maintained indefinitely in vitro, suggesting that they could be potentially used for cell–based therapies to treat or prevent retinal disease.
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