Kugler, Martina and Schlecht, Anja and Fuchshofer, Rudolf and Kleiter, Ingo and Aigner, Ludwig and Tamm, Ernst R. and Braunger, Barbara M. (2015) Heterozygous modulation of TGF-beta signaling does not influence Muller glia cell reactivity or proliferation following NMDA-induced damage. HISTOCHEMISTRY AND CELL BIOLOGY, 144 (5). pp. 443-455. ISSN 0948-6143, 1432-119X
Full text not available from this repository. (Request a copy)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. Muller glia cells have been discussed to represent a progenitor cell population in the adult retina. In the brain, TGF-beta signaling regulates the fate of stem cells; however, its role in the vertebrate retina is unclear. We therefore investigated whether manipulation of the TGF-beta signaling pathway is sufficient to promote Muller glia cell proliferation and subsequently their trans-differentiation into retinal neurons. To this end, we used mice with heterozygous deficiency of the essential TGF-beta receptor type II or of the inhibitory protein SMAD7, in order to down- or up-regulate the activity of TGF-beta 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 Muller glia cell reactivity, our findings indicate that a moderate modulation of TGF-beta signaling is not sufficient to provoke Muller glia cell proliferation. Hence, TGF-beta signaling in the retina might not be the essential causative factor to maintain mammalian Muller cells in a quiescent, non-proliferative state that prevents a stem cell-like function.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RETINAL STEM-CELLS; NEURAL REGENERATION; WNT/BETA-CATENIN; GANGLION-CELLS; GROWTH-FACTORS; RECEPTOR GENE; MOUSE RETINA; INJURY; ACTIVATION; MUTATIONS; TGF-beta signaling; Muller glia cells; Proliferation; Regeneration; Stem cells; NMDA |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 13:13 |
| Last Modified: | 07 May 2019 13:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4547 |
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