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Essential Role of mTOR Signaling in Human Retinal Pigment Epithelial Cell Regeneration After Laser Photocoagulation

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Abstract

This study assessed the role of mechanistic target of rapamycin (mTOR) pathway in the human adult retinal pigment epithelial (ARPE) cell response after laser photocoagulation (LP). The effect of mTOR inhibition on ARPE-19 cell was investigated by rapamycin treatment after LP. Cell viability and proliferation were explored using MTT and EdU assays, respectively. The expression of mTOR-related proteins and epithelial-mesenchymal transition (EMT) markers was verified by Western blot. Rapamycin retarded the LP area recovery in a dose-dependent manner by the 120 h, while LP+DMSO vehicle-treated cells completely restored the lesion zone (P ≤ 0.01). ARPE-19 cell viability is significantly lower in LP + rapamycin 80 and 160 ng/ml treated cultures compared to LP control at 120 h (P ≤ 0.001). LP control group demonstrated significantly more proliferative cells compared to untreated cells at the 72 and 120 h, whereas EdU-positive cell numbers in cultures treated with rapamycin at concentrations of 80 and 160 ng/ml were similar to baseline values (P ≤ 0.01). mTOR pathway activation is essential for regulation of the RPE cell migration and proliferation after LP. mTOR inhibition with rapamycin effectively blocks the migration and proliferation of the RPE cells. Our results demonstrate that mTOR has an important role in ARPE-19 cell as a regulator of cell behavior under stress conditions, suggesting that mTOR could be a promising therapeutic target for numerous retinal diseases.

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Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare (grant number HI17C0966); a grant from Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the ministry of Education, Science, and Technology (No.2016R1A2B4008376; Seoul, Republic of Korea); and also partially supported by the Soonchunhyang University research fund.

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Authors and Affiliations

  1. Department of Interdisciplinary Program in Biomedical Science, Soonchunhyang Graduate School, Bucheon Hospital, Bucheon, South Korea

    Sanjar Batirovich Madrakhimov, Jin Young Yang & Tae Kwann Park

  2. Laboratory for Translational Research on Retinal and Macular Degeneration, Soonchunhyang University Hospital Bucheon, Bucheon, South Korea

    Sanjar Batirovich Madrakhimov, Jin Young Yang, Ha Yan Park & Tae Kwann Park

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

    Tae Kwann Park

  4. Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan, Choongchungnam-do, South Korea

    Tae Kwann Park

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  1. Sanjar Batirovich Madrakhimov
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Correspondence to Tae Kwann Park.

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Madrakhimov, S.B., Yang, J.Y., Park, H.Y. et al. Essential Role of mTOR Signaling in Human Retinal Pigment Epithelial Cell Regeneration After Laser Photocoagulation. Lasers Med Sci 34, 1019–1029 (2019). https://doi.org/10.1007/s10103-018-2692-5

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