Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration.
| Title: | Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration. |
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| Authors: | Alaimo A; 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.; Liñares GG; 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.; Bujjamer JM; 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.; Gorojod RM; 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.; Alcon SP; 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.; Martínez JH; 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.; Baldessari A; 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.; Grecco HE; 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.; Kotler ML; 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. kotler@qb.fcen.uba.ar. |
| Source: | Archives of toxicology [Arch Toxicol] 2019 May; Vol. 93 (5), pp. 1401-1415. Date of Electronic Publication: 2019 Feb 18. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 0417615 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0738 (Electronic) Linking ISSN: 03405761 NLM ISO Abbreviation: Arch Toxicol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin, New York, Springer-Verlag. |
| MeSH Terms: | Light/*adverse effects ; Macular Degeneration/*pathology ; Retinal Pigment Epithelium/*pathology ; Retinoids/*metabolism; Apoptosis/physiology ; Macular Degeneration/etiology ; Mitochondrial Dynamics/physiology ; Reactive Oxygen Species/metabolism ; Retinal Pigment Epithelium/cytology ; Cell Line ; Humans |
| 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. |
| Grant Information: | PIP0771 International Consejo Nacional de Investigaciones Científicas y Técnicas (AR); PIP0519 International Consejo Nacional de Investigaciones Científicas y Técnicas (AR); PIP0653 International Consejo Nacional de Investigaciones Científicas y Técnicas; 20020130100212BA International Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires; 20020130200271BA International Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires; 20020170100755BA International Secretaria de Ciencia y Tecnica, Universidad de Buenos Aires; PICT2014-3658 International Fondo para la Investigación Científica y Tecnológica |
| Contributed Indexing: | Keywords: A2E; Age-related macular degeneration; Aging; Light pollution; Mitochondrial dynamics; Oxidative stress; Phototoxicity; RPE cells |
| Substance Nomenclature: | 0 (A2-E (N-retinylidene-N-retinylethanolamine)); 0 (Reactive Oxygen Species); 0 (Retinoids) |
| Entry Date(s): | Date Created: 20190220 Date Completed: 20200702 Latest Revision: 20200702 |
| Update Code: | 20260130 |
| DOI: | 10.1007/s00204-019-02409-6 |
| PMID: | 30778631 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't