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Forschungsdatenbank PMU-SQQUID

Heterozygous modulation of TGF-β signaling does not influence Müller glia cell reactivity or proliferation following NMDA-induced damage.
Kugler, M; Schlecht, A; Fuchshofer, R; Kleiter, I; Aigner, L; Tamm, ER; Braunger, BM
HISTOCHEM CELL BIOL. 2015; 144(5): 443-455.
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig

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.


Find related publications in this database (Keywords)

TGF-beta signaling
Muller glia cells
Proliferation
Regeneration
Stem cells
NMDA