July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Synergistic cytotoxicity and genotoxicity of polycyclic aromatic hydrocarbons and blue light in retinal pigment epithelium cells
Author Affiliations & Notes
  • Corinne Zinflou
    Faculty of Medicine, Laval University, Quebec, Quebec, Canada
    Centre Universitaire d'Ophtalmolgie, CHU de Quebec/Laval University research center, Quebec, Quebec, Canada
  • Patrick J Rochette
    Faculty of Medicine, Laval University, Quebec, Quebec, Canada
    Centre Universitaire d'Ophtalmolgie, CHU de Quebec/Laval University research center, Quebec, Quebec, Canada
  • Footnotes
    Commercial Relationships   Corinne Zinflou, None; Patrick Rochette, None
  • Footnotes
    Support  Fonds de recherche du Québec - Santé (FRQS)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 357. doi:
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      Corinne Zinflou, Patrick J Rochette; Synergistic cytotoxicity and genotoxicity of polycyclic aromatic hydrocarbons and blue light in retinal pigment epithelium cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):357.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Lesion to the retinal pigment epithelium (RPE) is a crucial event in age-related macular degeneration (AMD) development. Sunlight exposure and smoking are major environmental risk factors associated with AMD. High-energy visible blue light (HEV; 400-500 nm) is the most energetic and potentially harmful solar radiation reaching adults retina. On the other hand, cigarette smoke involves a large range of pollutants, with polycyclic aromatic hydrocarbons (PAH) being among the most toxic. Some PAH from cigarette smoke can absorb HEV light. We hypothesize that an interaction between PAH and HEV light in RPE could exacerbate the stress caused by either factor alone. This study thus investigates the combined effect of PAH and HEV light on confluent monolayers of retinal epithelial cells (ARPE19).

Methods : We measured the UV/visible absorption spectrum of 15 PAH and selected the indeno[1,2,3-cd]pyrene (IcdP), the one which absorbs more efficiently HEV wavelengths. Benzo[a]pyrene (BaP), the most studied PAH, does not significantly absorb HEV and was used as a control. ARPE19 cells were exposed to nanomolar concentrations of BaP or IcdP. PAH treated cells were then kept in the dark or irradiated with increasing sub-lethal doses of HEV light, using a setup that mimics the light spectrum normally reaching the retina. Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation and bulky DNA damage were assessed in each condition.

Results : In presence of sub-lethal quantities of IcdP (75 to 500 nM), sub-lethal doses of HEV light (≤ 320 J/cm2) trigger apoptosis in a dose-dependent way (p < 0.001). IcdP plus HEV (IcdP/HEV) exposure also leads to a synergistic generation of ROS in ARPE19 cells, for at least 6 h after the end of exposure. Efficient inhibition of IcdP/HEV-induced ROS by specific antioxidants only decreases death by 20 %. Finally, IcdP/HEV exposure induces a delayed accumulation of bulky adducts in DNA. None of these effects were observed with BaP.

Conclusions : Low amounts of IcdP synergize with HEV light to induce a phototoxic and genotoxic stress in ARPE19 cells. An oxidative stress results from this interaction. However, our results suggest that a mechanism other than oxidation essentially mediates IcdP/HEV-induced cell death. For smokers, this synergy between HEV and PAH may accelerate RPE cells loss and contribute to their greater risk of developing AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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