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Müller glia are a potential source of neural regeneration in the postnatal chicken retina

Abstract

The retina of warm-blooded vertebrates is believed to be incapable of neural regeneration. Here we provide evidence that the retina of postnatal chickens has the potential to generate new neurons. In response to acute damage, numerous Müller glia re-entered the cell cycle, and shortly thereafter, expressed CASH-1, Pax6 and Chx10, transcription factors expressed by embryonic retinal progenitors. These progenitor-like cells transiently expressed neurofilament. Newly formed cells became distributed throughout the inner and outer nuclear layers of the retina, and remained for at least three weeks after damage. Some of these newly formed cells differentiated into retinal neurons, a few formed Müller glia, and most remained undifferentiated, with continued expression of Pax6 and Chx10. These cells continued to proliferate when grown in culture, with some differentiating into retinal neurons or Müller glia. We propose that, in response to damage, Müller glia in the retina are a potential source of neural regeneration.

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Figure 1: Acute damage causes many cells in the chick retina to proliferate.
Figure 2: BrdU accumulates in microglia that express a lysosomal glycoprotein and Müller glia that express glutamine synthetase after acute damage.
Figure 3: The number of BrdU-labeled cells in toxin-damaged retina that are immunoreactive for glutamine synthetase decreases with increasing time after toxin treatment.
Figure 4: Many progenitor-like cells accumulate in the retina after acute damage.
Figure 5: Neurofilament-like protein is transiently expressed by proliferating Müller glia in toxin-damaged retina.
Figure 6: New neurons are generated in the chicken retina after acute damage.
Figure 7: Neurons and glia are produced by damage-induced progenitor-like cells in vitro.

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Acknowledgements

We thank B. Dierks for technical assistance, and W.K. Stell, D. Raible and J. Hurley for comments on the manuscript. The BrdU, Pax6, vimentin, neurofilament and LEP-100 antibodies developed by S.J. Kaufman, A. Kawakami, J. Sanes, J. Wood and D.M. Fambrough, respectively, were obtained from the DSHB developed under auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, Iowa 52242. This work was supported by fellowships to A.J.F from the Alberta Heritage Foundation for Medical Research, the Medical Research Council of Canada, and the Fight for Sight Foundation Research Division of Prevent Blindness America, and by grants to T.A.R. from the National Science Foundation, NSF9604843 the Foundation Fighting Blindness and NIH NS28308.

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Correspondence to Thomas A. Reh.

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Fischer, A., Reh, T. Müller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat Neurosci 4, 247–252 (2001). https://doi.org/10.1038/85090

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