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Histochemistry and Cell Biology

, Volume 144, Issue 5, pp 443–455 | Cite as

Heterozygous modulation of TGF-β signaling does not influence Müller glia cell reactivity or proliferation following NMDA-induced damage

  • Martina Kugler
  • Anja Schlecht
  • Rudolf Fuchshofer
  • Ingo Kleiter
  • Ludwig Aigner
  • Ernst R. Tamm
  • Barbara M. Braunger
Original Paper

Abstract

The stimulation of progenitor or stem cells proliferation in the retina could be a therapeutic avenue for the treatment of various ocular neurodegenerative disorders. Müller glia cells have been discussed to represent a progenitor cell population in the adult retina. In the brain, TGF-β signaling regulates the fate of stem cells; however, its role in the vertebrate retina is unclear. We therefore investigated whether manipulation of the TGF-β signaling pathway is sufficient to promote Müller glia cell proliferation and subsequently their trans-differentiation into retinal neurons. To this end, we used mice with heterozygous deficiency of the essential TGF-β receptor type II or of the inhibitory protein SMAD7, in order to down- or up-regulate the activity of TGF-β signaling, respectively. Excitotoxic damage was applied by intravitreal N-methyl-d-aspartate injection, and BrdU pulse experiments were used to label proliferative cells. Although we successfully stimulated Müller glia cell reactivity, our findings indicate that a moderate modulation of TGF-β signaling is not sufficient to provoke Müller glia cell proliferation. Hence, TGF-β signaling in the retina might not be the essential causative factor to maintain mammalian Müller cells in a quiescent, non-proliferative state that prevents a stem cell-like function.

Keywords

TGF-β signaling Müller glia cells Proliferation Regeneration Stem cells NMDA 

Notes

Acknowledgments

The authors would like to thank Elke Stauber, Angelika Pach, Margit Schimmel and Silvia Babl for their excellent technical assistance. This work was supported by Deutsche Forschungsgemeinschaft Grant FOR 1075 (TP9).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Martina Kugler
    • 1
  • Anja Schlecht
    • 1
  • Rudolf Fuchshofer
    • 1
  • Ingo Kleiter
    • 2
  • Ludwig Aigner
    • 3
  • Ernst R. Tamm
    • 1
  • Barbara M. Braunger
    • 1
  1. 1.Institute of Human Anatomy and EmbryologyUniversity of RegensburgRegensburgGermany
  2. 2.Department of NeurologySt. Josef-HospitalBochumGermany
  3. 3.Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center SalzburgParacelsus Medical UniversitySalzburgAustria

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