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Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration

Archives of Toxicology volume 93, pages 1401–1415 (2019)Cite this article

Abstract

Age-related macular degeneration (AMD) is a multifactorial retinal disease characterized by a progressive loss of central vision. Retinal pigment epithelium (RPE) degeneration is a critical event in AMD. It has been associated to A2E accumulation, which sensitizes RPE to blue light photodamage. Mitochondrial quality control mechanisms have evolved to ensure mitochondrial integrity and preserve cellular homeostasis. Particularly, mitochondrial dynamics involve the regulation of mitochondrial fission and fusion to preserve a healthy mitochondrial network. The present study aims to clarify the cellular and molecular mechanisms underlying photodamage-induced RPE cell death with particular focus on the involvement of defective mitochondrial dynamics. Light-emitting diodes irradiation (445 ± 18 nm; 4.43 mW/cm2) significantly reduced the viability of both unloaded and A2E-loaded human ARPE-19 cells and increased reactive oxygen species production. A2E along with blue light, triggered apoptosis measured by MC540/PI-flow cytometry and activated caspase-3. Blue light induced mitochondrial fusion/fission imbalance towards mitochondrial fragmentation in both non-loaded and A2E-loaded cells which correlated with the deregulation of mitochondria-shaping proteins level (OPA1, DRP1 and OMA1). To our knowledge, this is the first work reporting that photodamage causes mitochondrial dynamics deregulation in RPE cells. This process could possibly contribute to AMD pathology. Our findings suggest that the regulation of mitochondrial dynamics may be a valuable strategy for treating retinal degeneration diseases, such as AMD.

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Acknowledgements

This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET PIP 0771, PIP 0653) and University of Buenos Aires (UBACYT 20020130100212BA, 20020130200271BA and 20020170100755BA). J.M.B, R.M.G., S.P.A., J.H.M. are supported by a CONICET scholarship. A.A., G.G.L., A.B., H.E.G. and M.L.K. are researcher members at CONICET.

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  1. Guadalupe García Liñares and Juan Marco Bujjamer contributed equally to this work.

Authors and Affiliations

  1. Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Instituto de Química Biológica Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, 1428, Buenos Aires, Argentina

    Agustina Alaimo, Roxana Mayra Gorojod, Soledad Porte Alcon, Jimena Hebe Martínez & Mónica Lidia Kotler

  2. Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Unidad de Microanálisis y Métodos Físicos en Química Orgánica (UMYNFOR), CONICET-Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, 1428, Buenos Aires, Argentina

    Guadalupe García Liñares & Alicia Baldessari

  3. Departamento de Física, Facultad de Ciencias Exactas y Naturales, Instituto de Física de Buenos Aires (IFIBA), CONICET-Universidad de Buenos, Pabellón 1, Ciudad Universitaria, 1428, Buenos Aires, Argentina

    Juan Marco Bujjamer & Hernán Edgardo Grecco

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  1. Agustina Alaimo
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Alaimo, A., Liñares, G.G., Bujjamer, J.M. et al. Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration. Arch Toxicol 93, 1401–1415 (2019). https://doi.org/10.1007/s00204-019-02409-6

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Keywords

  • Age-related macular degeneration
  • RPE cells
  • Aging
  • Light pollution
  • Phototoxicity
  • A2E
  • Oxidative stress
  • Mitochondrial dynamics