title: 17-Alpha-estradiol ameliorating oxygen-induced retinopathy in a murine model.
abstract: OBJECTIVE
  Our aim was to explore the effects and mechanism of 17-alpha-estradiol (17α-E2) on oxygen-induced retinopathy (OIR) in a murine model.
  
  
  METHODS
  Newborn mice exposed to hyperoxia underwent subcutaneous injections of different doses of 17α-E2 from postnatal days (PND) 7 to 17. The retinal flat mounts were scored for avascular/total retinal area on PND 17. Vascular endothelial growth factor (VEGF), malondialdehyde (MDA) concentrations, and intensity, activity, and quality of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the retina were determined on PND 9, 13 (14), and 17.
  
  
  RESULTS
  The avascular area, which is found in retinas of hyperoxia-exposed pups but not in retinas of normoxia-exposed ones, was significantly smaller in retinas of 17α-E2-treated pups. MDA and VEGF concentrations and intensity, activity, and quality of NADPH oxidase were stable in retinas of normoxia pups on PND 9, 13 (14), and 17, whereas in retinas of hyperoxia-exposed and 17α-E2-treated pups, they fluctuated markedly. VEGF concentrations were lower in retinas of hyperoxia-exposed pups than in those of normoxia ones on PND 9. Elevated VEGF concentrations were found in retinas of 17α-E2-treated pups on PND 9 and in hyperoxia-exposed pups on PND 14 and 17. Low VEGF concentrations were found in retinas of 17α-E2-treated pups on PND 14 and 17. MDA concentrations and NADPH oxidase concentration and activity, which were higher in retinas of hyperoxia-exposed pups, were lower in retinas of 17α-E2-treated pups on PND 9, 13, and 17. The most effective outcome in retinas of 1.0 μg 17α-E2-treated pups was markedly reversed by ICI182780.
  
  
  CONCLUSIONS
  We found that 17α-E2 mitigates oxidative stress reactions and ameliorates OIR severity by decreasing NADPH oxidase expression and activity via the receptor and other pathways.
authors.affiliation: Department of Ophthalmology, The Second Affiliated Hospital of Xi'an Jiaotong University, #157 Xiwu Road, Xi'an 710004, Shanxi, People's Republic of China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Zhang
authors.forename: Nai-Xue
authors.initials: NX
authors.lastname: Sun
authors.forename: Hou-Cheng
authors.initials: HC
authors.lastname: Liang
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Xiao
authors.forename: Xian-Ning
authors.initials: XN
authors.lastname: Liu
authors.forename: Ya-Ni
authors.initials: YN
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002199:Capillary Permeability; D003911:Dextrans; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005452:Fluoresceins; D000077267:Fulvestrant; D006801:Humans; D007124:Immunoenzyme Techniques; D007231:Infant, Newborn; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D003911:Dextrans; D004965:Estrogen Antagonists; D004967:Estrogens; D005452:Fluoresceins; D042461:Vascular Endothelial Growth Factor A; C052526:fluorescein-dextran; C467480:vascular endothelial growth factor A, mouse; D000077267:Fulvestrant; D004958:Estradiol; D008315:Malondialdehyde; D019255:NADPH Oxidases; D010100:Oxygen