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Lasers in Medical Science

, Volume 34, Issue 3, pp 571–581 | Cite as

The role of Wnt/β-catenin signaling in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium after laser photocoagulation

  • In Hwan Cho
  • Seong Jun Park
  • Si Hyung Lee
  • Seung Kwan Nah
  • Ha Yan Park
  • Jin Young Yang
  • Sanjar Batirovich Madrakhimov
  • Jungmook LyuEmail author
  • Tae Kwann ParkEmail author
Original Article

Abstract

To investigate the role of Wnt/β-catenin signaling pathway in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) after laser photocoagulation. After differentiation of RPE cells from hiPSCs, laser photocoagulation was performed. Activation of Wnt/β-catenin signaling at days 1 and 5 after laser photocoagulation was evaluated by expression of β-catenin. Cell proliferation and alteration in cell-to-cell contact at day 5 after laser photocoagulation with or without Dickkopf-1 (Dkk-1) treatment were studied using ethynyl-2′-deoxyuridine (EdU) assay and zonula occludens-1 (ZO-1) expression analysis, respectively. The mRNA levels of Wnt genes at day 5 after laser photocoagulation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Activation of Wnt/β-catenin signaling at days 1 and 5 after laser photocoagulation was confirmed by β-catenin accumulation in the cytoplasm and nucleus of hiPSC-RPE. Many EdU-positive cells also expressed β-catenin, and the number of EdU-positive cells was decreased at day 5 after laser photocoagulation after Dkk-1 treatment, indicating that Wnt/β-catenin signaling mediated hiPSC-RPE proliferation. ZO-1 expression was not decreased with Dkk-1 treatment at day 5 after laser photocoagulation, indicating that Wnt/β-catenin signaling mediated hiPSC-RPE restoration. At day 5, after laser photocoagulation, mRNA levels of Wnt2b, Wnt3, Wnt5a, Wnt7a, and Wnt10b were increased. Wnt/β-catenin signaling has a crucial role in restoration of hiPSC-RPE proliferation after laser photocoagulation. Manipulation of Wnt/β-catenin signaling while elucidating the underlying mechanisms of RPE restoration might have a therapeutic potential in retinal degenerative diseases.

Keywords

Wnt/β-catenin signaling pathway Induced pluripotent stem cell Retinal pigment epithelium Laser photocoagulation 

Notes

Funding information

This study was financially supported by grants from Basic Science Research Program through the National Research Foundation of Korea (NRF) (No. 2016R1A2B4008376; Seoul, Republic of Korea). This work was partially supported by the Soonchunhyang University Research Fund.

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Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OphthalmologySoonchunhyang University Hospital CheonanCheonanRepublic of Korea
  2. 2.College of MedicineSoonchunhyang UniversityCheonanRepublic of Korea
  3. 3.Department of OphthalmologySoonchunhyang University Hospital BucheonBucheonRepublic of Korea
  4. 4.Department of Biomedical science, Graduate SchoolSoonchunhyang UniversityBucheonRepublic of Korea
  5. 5.Department of Medical ScienceKonyang UniversityDaejeonRepublic of Korea

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