TGFβ-signaling regulates the proliferation of Müller Glia-derived Progenitor Cells in the retina
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Date
2017-05
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The Ohio State University
Abstract
Müller glia cells in the retina can be stimulated to form Müller glia-derived progenitor cells (MGPCs) that can regenerate neurons. Müller glia are typically the support cells of the retina, but upon treatment with NMDA damage or consecutive doses of FGF2 may be stimulated to de-differentiate and form proliferating progenitor cells. The cell signaling pathways involved in the formation of MGPCs are beginning to be revealed, and a better understanding will help to develop novel strategies for treating retinal diseases in humans. This study aims to investigate the role of TGFβ-signaling in the proliferation and formation of MGPCs in the avian retina. The results of this study indicate that TGFβ signaling components are expressed in the retina. Immunohistochemistry shows that the transcription factor smad2 is localized to Müller glia nuclei in untreated retinas, but following NMDA and FGF2-treatment expression in the cytoplasm is increased. This suggests a decrease in TGFβ-signaling when MGPCs are known to form. We find that treatment with recombinant TGFβ2 reduces the formation of MGPCs in damaged retinas, as well as expression of stem cell markers Pax6, Klf4, and Egr1. Conversely, applying small molecule inhibitors to the pathway significantly increased the number of proliferating MGPCs in both damage and undamaged retinas. Consistent with these findings, inhibition of TGFβ-signaling also increased proliferation at the Ciliary Marginal Zone (CMZ), a separate progenitor cell population at the peripheral edge of the retina. We conclude that TGFβ is yet another pathway that influences the reprogramming of Müller glia into proliferating MGPCs.
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Keywords
retina, glia, regeneration, TGF-beta signaling