Transient exposure of rat pups to hyperoxia at normobaric and hyperbaric pressures does not cause retinopathy of prematurity.
We have shown that hyperoxia reduces brain damage in a rat model of hypoxia-ischemia. The purpose of this study was to examine the possibility of hyperoxia in inducing vision-threatening retinopathy. Two different experiments were conducted in this study. PART 1: seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% O2 at 37 degrees C). Pups were treated with 100% oxygen at 1 ATA, 1.5 ATA, and 3.0 ATA for a duration of 1 h. PART 2: Newborn rat pups were exposed to 100% oxygen at 1, 1.5, or 3.0 ATA for 1 h, the same treatment protocol used for brain protection after hypoxia-ischemia. Retinopathy was evaluated by the degree of neovascularization (measuring retinal vascular density), by the structural abnormalities (histology) in the retina, and by the expression of hypoxia-hyperoxia sensitive proteins including hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) at 24 h, 1, 2, and 10 weeks after hyperoxia exposure. Hyperoxic treatment at all pressures administered significantly reduced the hypoxia-ischemic-induced reduction in brain weight. Retinal vascular density measurements revealed no signs of neovascularization after hyperoxia exposure. There were also no abnormalities in the structure of the retina and no changes in the protein expression of HIF-1alpha and VEGF following hyperoxia exposure. Exposure to hyperoxia for 1 h at normobaric or hyperbaric pressures did not result in the structural changes or abnormal vascularization that is associated with retinopathy of prematurity, suggesting that hyperoxia is a safe treatment for hypoxic newborn infants.
Calvert
John W
JW
Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Zhou
Changman
C
Zhang
John H
JH
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001273:Atmosphere Exposure Chambers / Q000600:supply & distribution; D001274:Atmospheric Pressure; D001921:Brain / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006931:Hyperbaric Oxygenation; D018496:Hyperoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry / Q000379:methods; D007231:Infant, Newborn; D009474:Neurons / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects*; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000378:metabolism*; D013194:Staining and Labeling; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen