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Biomedicines 2017, 5(2), 25; doi:10.3390/biomedicines5020025

Implications of a Multi-Step Trigger of Retinal Regeneration in the Adult Newt

1
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba 305-8572, Japan
2
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba 305-8572, Japan
3
Graduate School of Engineering, Utsunomiya University, Yoto 7-1-2, Utsunomiya 321-8585, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Wenbin Deng
Received: 14 April 2017 / Revised: 16 May 2017 / Accepted: 17 May 2017 / Published: 20 May 2017
(This article belongs to the Section Neurologic Diseases)
View Full-Text   |   Download PDF [8577 KB, uploaded 20 May 2017]   |  

Abstract

The newt is an amazing four-limbed vertebrate that can regenerate various body parts including the retina. In this animal, when the neural retina (NR) is removed from the eye by surgery (retinectomy), both the NR and the retinal pigment epithelium (RPE) eventually regenerate through the process of reprogramming and proliferation of RPE cells. Thus far, we have pursued the onset mechanism of adult newt retinal regeneration. In this study, using an in vitro system, we found that both mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK and β-catenin were involved in cell cycle re-entry of RPE cells. MEK-ERK signaling activity in RPE cells was strengthened by retinectomy, and nuclear translocation of β-catenin in RPE cells was induced by attenuation of cell–cell contact, which was promoted by incision of the RPE or its treatment with ethylene glycol tetraacetic acid (EGTA). EGTA is a Ca2+ chelator that disrupts cadherin-mediated cell–cell adhesion. Reinforcement of MEK-ERK signaling activity was a prerequisite for nuclear translocation of β-catenin. These results suggest that retinectomy followed by attenuation of cell–cell contact may trigger cell cycle re-entry of RPE cells. This study, together with our previous findings concerning the proliferation and multipotency of adult newt RPE cells, provides insight into the mechanism of the multi-step trigger in which the onset of retinal regeneration in the adult newt is rigorously controlled. View Full-Text
Keywords: newt; retinal regeneration; retinal pigment epithelium; cell cycle; β-catenin; MEK; ERK newt; retinal regeneration; retinal pigment epithelium; cell cycle; β-catenin; MEK; ERK
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yasumuro, H.; Sakurai, K.; Toyama, F.; Maruo, F.; Chiba, C. Implications of a Multi-Step Trigger of Retinal Regeneration in the Adult Newt. Biomedicines 2017, 5, 25.

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