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

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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.

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Funding

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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Author notes

  1. In Hwan Cho and Seong Jun Park contributed equally to the work presented here and should therefore be regarded as equivalent first authors.

    Tae Kwann Park and Jungmook Lyu should be regarded as equivalent corresponding authors.

Authors and Affiliations

  1. Department of Ophthalmology, Soonchunhyang University Hospital Cheonan, Cheonan, Republic of Korea

    In Hwan Cho

  2. College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea

    Seong Jun Park & Tae Kwann Park

  3. Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, 170 Jomaru-ro, Wonmi-gu, Bucheon, 14584, Republic of Korea

    Si Hyung Lee, Seung Kwan Nah, Ha Yan Park & Tae Kwann Park

  4. Department of Biomedical science, Graduate School, Soonchunhyang University, Bucheon, Republic of Korea

    Jin Young Yang, Sanjar Batirovich Madrakhimov & Tae Kwann Park

  5. Department of Medical Science, Konyang University, 685 Gasoowon-dong, Seo-gu, Daejeon, 302-718, Republic of Korea

    Jungmook Lyu

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  1. In Hwan Cho
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Correspondence to Jungmook Lyu or Tae Kwann Park.

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Cho, I.H., Park, S.J., Lee, S.H. et al. The role of Wnt/β-catenin signaling in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium after laser photocoagulation. Lasers Med Sci 34, 571–581 (2019). https://doi.org/10.1007/s10103-018-2631-5

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  • DOI: https://doi.org/10.1007/s10103-018-2631-5

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