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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/cm 2 ) 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. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Registro:

Documento: Artículo
Título:Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration
Autor:Alaimo, A.; Liñares, G.G.; Bujjamer, J.M.; Gorojod, R.M.; Alcon, S.P.; Martínez, J.H.; Baldessari, A.; Grecco, H.E.; Kotler, M.L.
Filiación: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, Buenos Aires, 1428, Argentina
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, Buenos Aires, 1428, Argentina
Departamento de Física, Facultad de Ciencias Exactas y Naturales, Instituto de Física de Buenos Aires (IFIBA), CONICET-Universidad de Buenos, Pabellón 1, Ciudad Universitaria, Buenos Aires, 1428, Argentina
Palabras clave:A2E; Age-related macular degeneration; Aging; Light pollution; Mitochondrial dynamics; Oxidative stress; Phototoxicity; RPE cells
Año:2019
DOI: http://dx.doi.org/10.1007/s00204-019-02409-6
Título revista:Archives of Toxicology
Título revista abreviado:Arch. Toxicol.
ISSN:03405761
CODEN:ARTOD
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_03405761_v_n_p_Alaimo

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Citas:

---------- APA ----------
Alaimo, A., Liñares, G.G., Bujjamer, J.M., Gorojod, R.M., Alcon, S.P., Martínez, J.H., Baldessari, A.,..., Kotler, M.L. (2019) . 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.
http://dx.doi.org/10.1007/s00204-019-02409-6
---------- CHICAGO ----------
Alaimo, A., Liñares, G.G., Bujjamer, J.M., Gorojod, R.M., Alcon, S.P., Martínez, J.H., 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" . Archives of Toxicology (2019).
http://dx.doi.org/10.1007/s00204-019-02409-6
---------- MLA ----------
Alaimo, A., Liñares, G.G., Bujjamer, J.M., Gorojod, R.M., Alcon, S.P., Martínez, J.H., 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" . Archives of Toxicology, 2019.
http://dx.doi.org/10.1007/s00204-019-02409-6
---------- VANCOUVER ----------
Alaimo, A., Liñares, G.G., Bujjamer, J.M., Gorojod, R.M., Alcon, S.P., Martínez, J.H., 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. 2019.
http://dx.doi.org/10.1007/s00204-019-02409-6