Zusammenfassung
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 ...
Zusammenfassung
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.
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