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

Gu,Dandan; Wang,Songtao; Zhang,Shuai; Zhang,Peng; Zhou,Guomin

doi:10.3892/mmr.2017.7652

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
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Affiliations: Department of Anatomy, Histology and Embryology, Institute of Acupuncture Research, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China , Department of Integrative Medicine and Neurobiology, Institute of Acupuncture Research, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China , Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, Fudan University, Shanghai 200032, P.R. China
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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