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Open AccessArticle

Electrical Stimulation Induces Retinal Müller Cell Proliferation and Their Progenitor Cell Potential

1
Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
2
Department of Medical Biochemistry, Oslo University Hospital, 0372 Oslo, Norway
3
Department of Ophthalmology, Drammen Hospital, Vestre Viken Hospital Trust, 3004 Drammen, Norway
4
Institute of clinical medicine, University of Oslo, 0318 Oslo, Norway
5
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
6
Department of Oral Biology; Faculty of Dentistry, University of Oslo, 0372 Oslo, Norway
7
Department of Plastic and Reconstructive Surgery, Oslo University Hospital, 0027 Oslo, Norway
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 781; https://doi.org/10.3390/cells9030781
Received: 1 February 2020 / Revised: 12 March 2020 / Accepted: 17 March 2020 / Published: 23 March 2020
Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our previous study suggested that ES promoted retinal function and the proliferation of progenitor-like glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism remains obscure. Müller cells (MCs) are thought to be dormant residential progenitor cells that possess a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a ramp waveform of 20 Hz and 300 µA of current was effective at inducing mouse MC proliferation and enhancing their expression of progenitor cell markers, such as Crx (cone–rod homeobox) and Wnt7, as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing revealed that calcium signaling pathway activation was a key event, with a false discovery rate of 5.33 × 10−8 (p = 1.78 × 10−10) in ES-mediated gene profiling changes. Moreover, the calcium channel blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene induction, supporting a central role of ES-induced Ca2+ signaling in the MC changes. Our results suggest that low-current ES may present a convenient tool for manipulating MC behavior toward neuroregeneration and repair. View Full-Text
Keywords: electrical-stimulation; retina; glial cells; Müller cells; proliferation; retinitis pigmentosa electrical-stimulation; retina; glial cells; Müller cells; proliferation; retinitis pigmentosa
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Enayati, S.; Chang, K.; Achour, H.; Cho, K.-S.; Xu, F.; Guo, S.; Z. Enayati, K.; Xie, J.; Zhao, E.; Turunen, T.; Sehic, A.; Lu, L.; Utheim, T.P.; Chen, D.F. Electrical Stimulation Induces Retinal Müller Cell Proliferation and Their Progenitor Cell Potential. Cells 2020, 9, 781.

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