title: Heterozygous modulation of TGF-β signaling does not influence Müller glia cell reactivity or proliferation following NMDA-induced damage.
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.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kugler
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schlecht
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.affiliation: Department of Neurology, St. Josef-Hospital, Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Kleiter
authors.affiliation: Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Aigner
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany. Barbara.Braunger@vkl.uni-regensburg.de.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Braunger
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D058449:Intravitreal Injections; D051379:Mice; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D016202:N-Methylaspartate
keywords: Müller glia cells; NMDA; Proliferation; Regeneration; Stem cells; TGF-β signaling