title: Impairment of extramitochondrial oxidative phosphorylation in mouse rod outer segments by blue light irradiation.
abstract: Exposure to short wavelength light causes increased reactive oxygen intermediates production in the outer retina, particularly in the rod Outer Segments (OS). Consistently, the OS were shown to conduct aerobic ATP production through the ectopic expression of the electron transfer chain complexes I-IV and F1Fo-ATP synthase. These facts prompted us to verify if the oxidative phosphorylation in the OS is implied in the oxidative damage of the blue-light (BL) treated OS, in an organotypic model of mouse retina. Whole mouse eyeball cultures were treated with short wavelength BL (peak at 405 nm, output power 1 mW/cm(2)) for 6 h. Immunogold transmission electron microscopy confirmed the expression of Complex I and F1Fo-ATP synthase in the OS. In situ histochemical assays on unfixed sections showed impairment of respiratory Complexes I and II after BL exposure, both in the OS and IS, utilized as a control. Basal O2 consumption and ATP synthesis were impaired in the OS purified from blue-light irradiated eyeball cultures. Electron transfer capacity between Complex I and II as well as activity of Complexes I and II was decreased in blue-light irradiated purified OS. The severe malfunctioning of the OS aerobic respiratory capacity after 6 h BL treatment may be the consequence of a self-induced damage. BL exposure would cause an initial over-functioning of both the phototransduction and respiratory chain, with reactive oxygen species production. In a self-renewal vicious cycle, membrane and protein oxidative damage, proton leakage and uncoupling, would impair redox chains, perpetuating the damage and causing hypo-metabolism with eventual apoptosis of the rod. Data may shed new light on the rod-driven retinopathies such as Age Related Macular Degeneration, of which blue-light irradiated retina represents a model.
authors.affiliation: Department of Pharmacy-DIFAR, Biochemistry and Physiology Lab, University of Genoa, V.le Benedetto XV 3, Genova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calzia
authors.affiliation: Department of Pharmacy-DIFAR, Biochemistry and Physiology Lab, University of Genoa, V.le Benedetto XV 3, Genova, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Panfoli
authors.affiliation: Department of Anatomy, Technische Universitaet (TU) Dresden, Dresden, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Heinig
authors.affiliation: Department of Anatomy, Technische Universitaet (TU) Dresden, Dresden, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schumann
authors.affiliation: CRTD Center for Regenerative Therapy Dresden, Dresden, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Ader
authors.affiliation: Clinica Oculistica, (Di.N.O.G.M.I.) University of Genoa, IRCCS Azienda Ospedaliera Universitaria San Martino - IST), V.le Benedetto XV 6, Genova, Italy.
authors.forename: Carlo Enrico
authors.initials: CE
authors.lastname: Traverso
authors.affiliation: Department of Anatomy, Technische Universitaet (TU) Dresden, Dresden, Germany.
authors.forename: Richard H W
authors.initials: RH
authors.lastname: Funk
authors.affiliation: Department of Anatomy, Technische Universitaet (TU) Dresden, Dresden, Germany.
authors.forename: Cora
authors.initials: C
authors.lastname: Roehlecke
mesh_terms: D000818:Animals; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism*; D005260:Female; D008027:Light; D008297:Male; D051379:Mice; D010085:Oxidative Phosphorylation / Q000528:radiation effects*; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000201:enzymology*
chemical_list: D045222:Electron Transport Chain Complex Proteins; D006180:Proton-Translocating ATPases
keywords: ATP synthase; Blue light; Electron transport chain; Reactive oxidative phosphorylation oxygen intermediates