title: Exogenous Superoxide Dismutase Mimetic Without Scavenging H2O2 Causes Photoreceptor Damage in a Rat Model for Oxygen-Induced Retinopathy.
abstract: OBJECTIVE
  Frequent, brief intermittent episodes of hypoxia (IH) during hyperoxia increase reactive oxygen species in the immature retina with compromised antioxidant systems, thus leading to oxygen-induced retinopathy (OIR). We examined the hypothesis that early exposure to a mimetic of superoxide dismutase (SOD), the first line of defense against oxidative stress, will decrease IH-induced reactive oxygen species (ROS) and prevent severe OIR in our rat model.
  
  
  METHODS
  To test this hypothesis, newborn rats (P0) were exposed to IH consisting of alternating cycles of 50% O₂ with brief hypoxia (12% O₂) until P14 during which they were treated with a single daily intraperitoneal (IP) dose of MnTBAP (a SOD mimetic) at 1.0, 5.0, or 10.0 mg/kg on P0, P1, and P2. A saline-treated group served as vehicle controls. Groups were analyzed following IH at P14 or allowed to recover in room air (RA) until P21. Control littermates were raised in RA with all conditions identical except for inspired O₂. Ocular assessment of OIR severity, oxidative stress, angiogenesis, antioxidant activity, and oxidative phosphorylation (OXPHOS) were conducted at P14 and P21.
  
  
  RESULTS
  Collectively, the data show increased oxidative stress and angiogenesis with MnTBAP, which was associated with photoreceptor damage, retinal characteristics consistent with severe OIR, and changes in genes regulating OXPHOS.
  
  
  CONCLUSIONS
  In the setting of IH, the use of exogenous SOD mimetics must be combined with H₂O₂ scavengers in order to prevent photoreceptor damage and severe OIR.
authors: Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California-Irvine, Irvine, California, United States.
authors: Shamin
authors: S
authors: Jivabhai Patel
authors: Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California-Irvine, Irvine, California, United States.
authors: Fayez
authors: F
authors: Bany-Mohammed
authors: Department of Ophthalmology, State University of New York, Downstate Medical Center, New York, New York, United States State University of New York Eye Institute, New York, New York, United States.
authors: Lois
authors: L
authors: McNally
authors: Department of Pediatrics, State University of New York, Downstate Medical Center, New York, New York, United States.
authors: Gloria B
authors: GB
authors: Valencia
authors: Department of Ophthalmology, State University of New York, Downstate Medical Center, New York, New York, United States State University of New York Eye Institute, New York, New York, United States.
authors: Douglas R
authors: DR
authors: Lazzaro
authors: Department of Ophthalmology, State University of New York, Downstate Medical Center, New York, New York, United States.
authors: Jacob V
authors: JV
authors: Aranda
authors: Department of Ophthalmology, State University of New York, Downstate Medical Center, New York, New York, United States.
authors: Kay D
authors: KD
authors: Beharry
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018496:Hyperoxia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012160:Retina / Q000503:physiopathology*; D012178:Retinopathy of Prematurity / Q000503:physiopathology*; D013482:Superoxide Dismutase / Q000502:physiology*
chemical_list: D008665:Metalloporphyrins; D017382:Reactive Oxygen Species; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase
keywords: antioxidants; intermittent hypoxia; oxygen-induced retinopathy; retina