Touhami, S;
Beguier, F;
Augustin, S;
Charles-Messance, H;
Vignaud, L;
Nandrot, EF;
Reichman, S;
... Sennlaub, F; + view all
(2018)
Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation.
Journal of Neuroinflammation
, 15
, Article 85. 10.1186/s12974-018-1106-8.
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Abstract
BACKGROUND: The retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important barrier and immuno-suppressive functions in the eye. We have previously shown that acute stimulation of RPE cells by tumor necrosis factor alpha (TNFα) downregulates the expression of OTX2 (Orthodenticle homeobox 2) and dependent RPE genes. We here investigated the long-term effects of TNFα on RPE cell morphology and key functions in vitro. METHODS: Primary porcine RPE cells were exposed to TNFα (at 0.8, 4, or 20 ng/ml per day) for 10 days. RPE cell morphology, phagocytosis, barrier- and immunosuppressive-functions were assessed. RESULTS: Chronic (10 days) exposure of primary RPE cells to TNFα increases RPE cell size and polynucleation, decreases visual cycle gene expression, impedes RPE tight-junction organization and transepithelial resistance, and decreases the immunosuppressive capacities of the RPE. TNFα-induced morphological- and transepithelial-resistance changes were prevented by concomitant Transforming Growth Factor β inhibition. CONCLUSIONS: Our results indicate that chronic TNFα-exposure is sufficient to alter RPE morphology and impede cardinal features that define the differentiated state of RPE cells with striking similarities to the alterations that are observed with age in neurodegenerative diseases such as age-related macular degeneration.
| Type: | Article |
|---|---|
| Title: | Chronic exposure to tumor necrosis factor alpha induces retinal pigment epithelium cell dedifferentiation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s12974-018-1106-8 |
| Publisher version: | https://doi.org/10.1186/s12974-018-1106-8 |
| Language: | English |
| Additional information: | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
| Keywords: | Retinal pigment epithelium, Tumor necrosis factor alpha, Transforming growth factor beta, Age-related macular degeneration, Neuroinflammation, Neurodegenerative disease |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10053699 |
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