Abstract
Lesion to the retinal pigment epithelium (RPE) is a crucial event in the development of age-related macular degeneration (AMD), the leading cause of blindness in industrialized countries. Tobacco smoking and high-energy visible blue (HEV; 400–500 nm) light exposure are major environmental risk factors for AMD. Individually, they have been shown to cause damage to the RPE. Tobacco smoke contains toxic polycyclic aromatic hydrocarbons (PAH) that can accumulate in RPE and which absorb HEV light. It can thus be postulated that the interaction between both factors in RPE cells can have a synergic toxic effect to the RPE. To test this hypothesis, cultured human RPE cells (ARPE19) were treated with nanomolar concentrations of benzo[a]pyrene (BaP) or indeno[1,2,3-cd]pyrene (IcdP), then exposed to HEV light using an irradiation system that mimics the solar spectrum normally transmitted to the retina through the human ocular media. Using mitochondrial network morphology changes and key features of AMD-related RPE defects such as apoptotic cell death and oxidative stress, we demonstrate that a synergistic phototoxicity is generated when nanomolar concentrations (≤ 500 nM) of IcdP interact with sub-lethal amounts of HEV light. Indeed, we found IcdP to be at least 3000 times more toxic for RPE cells when irradiated with HEV light. This synergy translates into disruption of mitochondrial network, ROS enhanced accumulation and apoptosis of RPE cells. Our results underline an important interplay between two environmental risk factors involved in AMD progression and strongly indicate that IcdP, upon interaction with HEV light, may initiate the biological mechanisms underlying the association between cigarette smoking and AMD-related RPE degeneration.
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Acknowledgements
The authors are grateful to the Institut National d’Optique (INO) (Québec, Canada) for technical support. This work was supported by a Grant from the Canadian Institutes of Health Research (CIHR, MOP-133719) to P.J.R. P.J.R. is a research scholar from the Fonds de Recherche du Québec – Santé (FRQ-S).
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CZ: experiment conception and design, data collection, analysis and interpretation of data, manuscript writing, and critical revision. PJR: experiment conception and design, critical revision.
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Zinflou, C., Rochette, P.J. Absorption of blue light by cigarette smoke components is highly toxic for retinal pigmented epithelial cells. Arch Toxicol 93, 453–465 (2019). https://doi.org/10.1007/s00204-018-2344-3
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DOI: https://doi.org/10.1007/s00204-018-2344-3