title: Degeneration modulates retinal response to transient exogenous oxidative injury.
abstract: OBJECTIVE
  Oxidative injury is involved in retinal and macular degeneration. We aim to assess if retinal degeneration associated with genetic defect modulates the retinal threshold for encountering additional oxidative challenges.
  
  
  METHODS
  Retinal oxidative injury was induced in degenerating retinas (rd10) and in control mice (WT) by intravitreal injections of paraquat (PQ). Retinal function and structure was evaluated by electroretinogram (ERG) and histology, respectively. Oxidative injury was assessed by immunohistochemistry for 4-Hydroxy-2-nonenal (HNE), and by Thiobarbituric Acid Reactive Substances (TBARS) and protein carbonyl content (PCC) assays. Anti-oxidant mechanism was assessed by quantitative real time PCR (QPCR) for mRNA of antioxidant genes and genes related to iron metabolism, and by catalase activity assay.
  
  
  RESULTS
  Three days following PQ injections (1 µl of 0.25, 0.75, and 2 mM) the average ERG amplitudes decreased more in the WT mice compared with the rd10 mice. For example, following 2 mM PQ injection, ERG amplitudes reduced 1.84-fold more in WT compared with rd10 mice (p = 0.02). Injection of 4 mM PQ resulted in retinal destruction. Altered retina morphology associated with PQ was substantially more severe in WT eyes compared with rd10 eyes. Oxidative injury according to HNE staining and TBARS assay increased 1.3-fold and 2.1-fold more, respectively, in WT compared with rd10 mice. At baseline, prior to PQ injection, mRNA levels of antioxidant genes (Superoxide Dismutase1, Glutathione Peroxidase1, Catalase) and of Transferrin measured by quantitative PCR were 2.1-7.8-fold higher in rd10 compared with WT mice (p<0.01 each), and catalase activity was 1.7-fold higher in rd10 (p = 0.0006).
  
  
  CONCLUSIONS
  This data suggests that degenerating rd10 retinas encounter a relatively lower degree of damage in response to oxidative injury compared with normal retinas. Constitutive up-regulation of the oxidative defense mechanism in degenerating retinas may confer such relative protection from oxidative injury.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel ; Department of Cellular Biochemistry and Human Genetics, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Lederman
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Hagbi-Levi
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Michelle
authors.initials: M
authors.lastname: Grunin
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel ; Department of Cellular Biochemistry and Human Genetics, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Alexey
authors.initials: A
authors.lastname: Obolensky
authors.affiliation: Department of Cellular Biochemistry and Human Genetics, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Eduard
authors.initials: E
authors.lastname: Berenshtein
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.affiliation: Department of Cellular Biochemistry and Human Genetics, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Mordechai
authors.initials: M
authors.lastname: Chevion
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
authors.forename: Itay
authors.initials: I
authors.lastname: Chowers
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004596:Electroretinography; D007150:Immunohistochemistry; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D010269:Paraquat / Q000009:adverse effects; D050050:Protein Carbonylation; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000187:drug effects / Q000293:injuries*; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000447:Aldehydes; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; C027576:4-hydroxy-2-nonenal; D010269:Paraquat