Absorption of blue light by cigarette smoke components is highly toxic for retinal pigmented epithelial cells
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.
KeywordsAge-related macular degeneration Polycyclic aromatic hydrocarbons Benzo[a]pyrene Indeno[1,2,3-cd]pyrene High energy visible blue light Oxidative stress
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).
CZ: experiment conception and design, data collection, analysis and interpretation of data, manuscript writing, and critical revision. PJR: experiment conception and design, critical revision.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Bertram KM, Baglole CJ, Phipps RP, Libby RT (2009) Molecular regulation of cigarette smoke induced-oxidative stress in human retinal pigment epithelial cells: implications for age-related macular degeneration. Am J Physiol Cell Physiol 297:C1200–C1210. https://doi.org/10.1152/ajpcell.00126.2009 CrossRefGoogle Scholar
- Boettner EA, Wolter JR (1962) Transmission of the ocular media Invest. Ophthalmol Vis Sci 1:776–783Google Scholar
- Dabestani R, Ivanov IN (1999) A compilation of physical, spectroscopic and photophysical properties of polycyclic aromatic hydrocarbons. Photochem Photobiol 70:10–34Google Scholar
- Espinosa-Heidmann DG, Suner IJ, Catanuto P, Hernandez EP, Marin-Castano ME, Cousins SW (2006) Cigarette smoke-related oxidants and the development of sub-RPE deposits in an experimental animal model of dry. AMD Invest Ophthalmol Vis Sci 47:729–737. https://doi.org/10.1167/iovs.05-0719 CrossRefGoogle Scholar
- Feher J, Kovacs I, Artico M, Cavallotti C, Papale A, Balacco Gabrieli C (2006) Mitochondrial alterations of retinal pigment epithelium in age-related macular degeneration. Neurobiol Aging 27:983–993. https://doi.org/10.1016/j.neurobiolaging.2005.05.012 CrossRefGoogle Scholar
- Fritsche LG, Fariss RN, Stambolian D, Abecasis GR, Curcio CA, Swaroop A (2014) Age-related macular degeneration: genetics and biology coming together. Annu Rev Genom Hum Genet 15:151–171. https://doi.org/10.1146/annurev-genom-090413-025610 CrossRefGoogle Scholar
- Kontush A, Finckh B, Karten B, Kohlschutter A, Beisiegel U (1996) Antioxidant and prooxidant activity of alpha-tocopherol in human plasma and low density lipoprotein. J Lipid Res 37:1436–1448Google Scholar
- Lerman S (1980) Radiant energy and the eye. Macmillan, New YorkGoogle Scholar
- Pleil JD, Stiegel MA, Sobus JR, Tabucchi S, Ghio AJ, Madden MC (2010) Cumulative exposure assessment for trace-level polycyclic aromatic hydrocarbons (PAHs) using human blood and plasma analysis. J Chromatogr B Anal Technol Biomed Life Sci 878:1753–1760. https://doi.org/10.1016/j.jchromb.2010.04.035 CrossRefGoogle Scholar
- Sparrow JR, Nakanishi K, Parish CA (2000) The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest Ophthalmol Vis Sci 41:1981–1989Google Scholar
- Wang S, Sheng Y, Feng M, Leszczynski J, Wang L, Tachikawa H, Yu H (2007) Light-induced cytotoxicity of 16 polycyclic aromatic hydrocarbons on the US EPA priority pollutant list in human skin HaCaT keratinocytes: relationship between phototoxicity and excited state properties. Environ Toxicol 22:318–327. https://doi.org/10.1002/tox.20241 CrossRefGoogle Scholar
- Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY (2014) Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2:e106–e116. https://doi.org/10.1016/S2214-109X(13)70145-1 CrossRefGoogle Scholar