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Jan Wijnholds, Pete Quinn, Ditte M. Lundvig, Lucie P. Pellissier, Berend Hooibrink, Robert M. Hoek; Adult Müller Glia Cells Are Efficient Progenitor Cells For Starburst Amacrine Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3972.
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© ARVO (1962-2015); The Authors (2016-present)
Müller glia cells in fish and birds are potential progenitor cells for retinal neurons, but mammalian Müller glia cells are limited in generating neurons in situ. We have studied the capacity of highly purified Müller glia cells to form, upon retinal transplantation, retinal neurons.
Mouse Müller glia cells were dissociated, purified by fluorescence-activated cell sorting (FACS) by use of cell surface antigens and vital dye cell trackers, and transplanted subretinally or intravitreously into the mouse retina. Immunohistochemistry was performed on retinal sections and whole-mount preparations.
Immunocytochemical analysis of sorted Müller glia cells showed that these cells express markers for Müller glia cells immediately after sort. Upon subretinal or intravitreal transplantation of unmanipulated cells in Crb1-/- or wild-type recipients, these cells efficiently migrate towards the inner face of the inner nuclear layer (INL) and to the ganglion cell layer (GCL), within 9 days. The transplanted Müller glia cells change cell fate; they re-differentiate into choline-acetyl transferase (ChAT) positive starburst amacrine cells (SAC). Whole mount staining and mosaics analysis indicated that the projection and mosaics pattern of the transplanted cells is similar to that of resident SACs. The transplanted cells project to the sub-layer s1/2 and s4/5 in the inner plexiform layer (IPL). Furthermore, we showed that transplantation into wild type mice also led to the re-differentiation of these cells into SACs and efficient migration into the retina. In addition, we have initiated experiments to culture these cells enabling their manipulation by applying factors to guide their differentiation behavior, in order to obtain other retinal cell types upon transplantation.
Mammalian Müller glia cells can be purified by FACS using cell surface antigens. Upon retinal transplantation, the mouse Müller glia cells efficiently re-differentiate into retinal neurons. Experiments to repeat the results with human Müller glia cells are ongoing.
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