Open Access

Directed transdifferentiation of Müller glial cells to photoreceptors using the sonic hedgehog signaling pathway agonist purmorphamine

  • Authors:
    • Dandan Gu
    • Songtao Wang
    • Shuai Zhang
    • Peng Zhang
    • Guomin Zhou
  • View Affiliations

  • Published online on: September 28, 2017     https://doi.org/10.3892/mmr.2017.7652
  • Pages:7993-8002
  • Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Specification of distinct cell types from Müller glial cells is key to the potential application of endogenous repair in retinal regeneration. Sonic hedgehog (SHH) has been established as a potent mitogen for rat Müller glial cells, which also induces Müller glial cells to dedifferentiate and adopt the phenotype of rod photoreceptors. The present study investigated the effects of purmorphamine, a small molecule that activates the SHH‑pathway, in the proliferation, dedifferentiation and transdifferentiation of Müller glial cells, as determined by several methods including immunofluorescence, polymerase chain reaction and western blotting. It was demonstrated that it may be able to replace SHH for the regeneration of retinal neurons. Purmorphamine was revealed to stimulate the proliferation of Müller glial cells by increasing the expression of cyclin D1 and cyclin D3. In addition, purmorphamine‑treated Müller glial cells were induced to dedifferentiate by inducing the expression of progenitor‑specific markers; subsequently differentiating into rod‑like photoreceptors. Intraocular injection of purmorphamine promoted the activation of Müller glial cells, and in turn, the production of rod‑like photoreceptors in acute damaged retina. These results suggested that the endogenous neurogenic capacity of retinal Müller glial cells may be enhanced by this small molecular agonist of the SHH signaling pathway.

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Journal Cover

December 2017
Volume 16 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

2016 Impact Factor: 1.692
Ranked #19/128 Medicine Research and Experimental
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APA
Gu, D., Wang, S., Zhang, S., Zhang, P., & Zhou, G. (2017). Directed transdifferentiation of Müller glial cells to photoreceptors using the sonic hedgehog signaling pathway agonist purmorphamine. Molecular Medicine Reports, 16, 7993-8002. https://doi.org/10.3892/mmr.2017.7652
MLA
Gu, D., Wang, S., Zhang, S., Zhang, P., Zhou, G."Directed transdifferentiation of Müller glial cells to photoreceptors using the sonic hedgehog signaling pathway agonist purmorphamine". Molecular Medicine Reports 16.6 (2017): 7993-8002.
Chicago
Gu, D., Wang, S., Zhang, S., Zhang, P., Zhou, G."Directed transdifferentiation of Müller glial cells to photoreceptors using the sonic hedgehog signaling pathway agonist purmorphamine". Molecular Medicine Reports 16, no. 6 (2017): 7993-8002. https://doi.org/10.3892/mmr.2017.7652