|   | 
Author (up) Alaimo, A.; Linares, G.G.; Bujjamer, J.M.; Gorojod, R.M.; Alcon, S.P.; Martinez, J.H.; Baldessari, A.; Grecco, H.E.; Kotler, M.L.
Title Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration Type Journal Article
Year 2019 Publication Archives of Toxicology Abbreviated Journal Arch Toxicol
Volume in press Issue Pages
Keywords Vision
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.
Address Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Instituto de Quimica Biologica Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Pabellon 2, Ciudad Universitaria, 1428, Buenos Aires, Argentina. kotler@qb.fcen.uba.ar
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0340-5761 ISBN Medium
Area Expedition Conference
Notes PMID:30778631 Approved no
Call Number GFZ @ kyba @ Serial 2229
Permanent link to this record