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Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells

Marie, M; Bigot, K; Angebault, C; Barrau, C; Gondouin, P; Pagan, D; Fouquet, S; ... Picaud, S; + view all (2018) Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells. Cell Death and Disease , 9 , Article 287. 10.1038/s41419-018-0331-5. Green open access

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Abstract

Aims: Blue light is an identified risk factor for age-related macular degeneration (AMD). We investigated oxidative stress markers and mitochondrial changes in A2E-loaded retinal pigment epithelium cells under the blue-green part of the solar spectrum that reaches the retina to better understand the mechanisms underlying light-elicited toxicity. Results: Primary retinal pigment epithelium cells were loaded with a retinal photosensitizer, AE2, to mimic aging. Using a custom-made illumination device that delivers 10 nm-wide light bands, we demonstrated that A2E-loaded RPE cells generated high levels of both hydrogen peroxide (H2O2) and superoxide anion (O2•-) when exposed to blue-violet light. In addition, they exhibited perinuclear clustering of mitochondria with a decrease of both their mitochondrial membrane potential and their respiratory activities. The increase of oxidative stress resulted in increased levels of the oxidized form of glutathione and decreased superoxide dismutase (SOD) and catalase activities. Furthermore, mRNA expression levels of the main antioxidant enzymes (SOD2, catalase, and GPX1) also decreased. Conclusions: Using an innovative illumination device, we measured the precise action spectrum of the oxidative stress mechanisms on A2E-loaded retinal pigment epithelium cells. We defined 415-455 nm blue-violet light, within the solar spectrum reaching the retina, to be the spectral band that generates the highest amount of reactive oxygen species and produces the highest level of mitochondrial dysfunction, explaining its toxic effect. This study further highlights the need to filter these wavelengths from the eyes of AMD patients.

Type: Article
Title: Light action spectrum on oxidative stress and mitochondrial damage in A2E-loaded retinal pigment epithelium cells
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41419-018-0331-5
Publisher version: http://doi.org/10.1038/s41419-018-0331-5
Language: English
Additional information: Copyright © 2018 The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
URI: https://discovery.ucl.ac.uk/id/eprint/10053731
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