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G.A. Limb, J.M. Lawrence, D.J. Keegan, T.A. Reh, P.J. Coffey, P.J. Luthert, P.T. Khaw; Müller Glial Cells From Adult Human Retina Exhibit Neural Stem Cell Characteristics And Prevent Loss Of Visual Function And Retinal Degeneration In The RCS Rat . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5387.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the stem cell characteristics of immortalized adult human Müller cells and to determine their ability to preserve visual function and retinal integrity when transplanted into eyes of RCS rats susceptible to retinal degeneration. Methods: Various preparations of immortalized human Müller cells were cultured on extracellular matrix coated plates in the presence of growth and differentiating factors. After various times in culture, cells were examined for morphological changes, ability to form neurospheres, and expression of markers for neural progenitors and retinal neurons. Cell suspensions of the immortalized human Müller cell line MIO–M1 were also transplanted into the subretinal space of 4 week old RCS rats, and visual function was examined by head–tracking experiments at regular intervals after transplantation. Retinal morphology and human Müller cell distribution, as judged by staining with anti–human mitochondria antibodies, were analyzed after ocular enucleation of terminally anesthetized rats. Results: Immortalized human Müller cell preparations exhibit characteristics of neural retinal progenitors as identified by their ability to form neurospheres and exhibit morphological features of neural cells in vitro. Confocal microscopy analysis showed that, under various conditions in culture, these cells express markers of neural progenitors, such as Nestin and ßIII Tubulin, and markers of differentiated retinal neurons, including Calretinin, Brn 5.0, Neuron–specific Enolase, Thy–1, Peripherin, Rhodopsin and 70kDa Neurofilament protein. When transplanted into RCS rats, Müller derived progenitors preserved visual function and maintained retinal integrity up to 15 weeks post–transplantation. Conclusions: We have identified a population of Müller cells in the adult human eye that exhibit characteristics of neural progenitors in vitro and that preserve visual function and maintain retinal integrity in an in vivo experimental model. These findings pave the way for the investigation of the potential use of Müller progenitor cells in human retinal transplantation to regenerate visual function lost by disease.
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