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Int. J. Mol. Sci. 2019, 20(4), 926; https://doi.org/10.3390/ijms20040926

Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation

1
Department of Biochemistry and Molecular Biology, University of Debrecen, Faculty of Medicine, 4032 Debrecen, Hungary
2
Tampere University, Faculty of Medicine and Health Technology, 33014 Tampere, Finland
3
School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, 70211 Kuopio, Finland
4
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70211 Kuopio, Finland
5
Department of Ophthalmology, Kuopio University Hospital, 70029 Kuopio, Finland
6
Department of Ophthalmology, Justus-Liebig-University Giessen, Eye Clinic, University Hospital Giessen and Marburg GmbH, Campus Giessen, 35390 Giessen, Germany
7
Department of Ophthalmology, Faculty of Medicine, University of Szeged, 6720 Szeged, Hungary
8
Center for Eye Research, Department of Ophthalmology, Oslo University Hospital and University of Oslo, Kirkeveien 166, 0450 Oslo, Norway
*
Author to whom correspondence should be addressed.
Received: 7 November 2018 / Revised: 19 December 2018 / Accepted: 13 February 2019 / Published: 20 February 2019
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD))
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Abstract

Inefficient removal of dying retinal pigment epithelial (RPE) cells by professional phagocytes can result in debris formation and development of age-related macular degeneration (AMD). Chronic oxidative stress and inflammation play an important role in AMD pathogenesis. Only a few well-established in vitro phagocytosis assay models exist. We propose human embryonic stem cell-derived-RPE cells as a new model for studying RPE cell removal by professional phagocytes. The characteristics of human embryonic stem cells-derived RPE (hESC-RPE) are similar to native RPEs based on their gene and protein expression profile, integrity, and barrier properties or regarding drug transport. However, no data exist about RPE death modalities and how efficiently dying hESC-RPEs are taken upby macrophages, and whether this process triggers an inflammatory responses. This study demonstrates hESC-RPEs can be induced to undergo anoikis or autophagy-associated cell death due to extracellular matrix detachment or serum deprivation and hydrogen-peroxide co-treatment, respectively, similar to primary human RPEs. Dying hESC-RPEs are efficiently engulfed by macrophages which results in high amounts of IL-6 and IL-8 cytokine release. These findings suggest that the clearance of anoikic and autophagy-associated dying hESC-RPEs can be used as a new model for investigating AMD pathogenesis or for testing the in vivo potential of these cells in stem cell therapy. View Full-Text
Keywords: age-related macular degeneration; anoikis; autophagy; hESC-RPE; inflammation; macrophages; phagocytosis; triamcinolone age-related macular degeneration; anoikis; autophagy; hESC-RPE; inflammation; macrophages; phagocytosis; triamcinolone
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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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Szatmári-Tóth, M.; Ilmarinen, T.; Mikhailova, A.; Skottman, H.; Kauppinen, A.; Kaarniranta, K.; Kristóf, E.; Lytvynchuk, L.; Veréb, Z.; Fésüs, L.; Petrovski, G. Human Embryonic Stem Cell-Derived Retinal Pigment Epithelium-Role in Dead Cell Clearance and Inflammation. Int. J. Mol. Sci. 2019, 20, 926.

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