title: Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice.
abstract: OBJECTIVE
  Glutathione peroxidase-1 (GPx1) is highly expressed during normal retinal maturation; however, its role in retinopathy of prematurity (ROP) is not fully understood. We postulated that GPx1 plays an important role in protecting the premature retina from oxidative injury in a mouse model of ROP.
  
  
  METHODS
  ROP was induced in wild-type (WT) and GPx1 knockout (KO) mice by exposing neonatal mice to 75% oxygen from postnatal days 7 to 11, followed by 1 week of room air. Structural effects of ROP were evaluated by retinal histology, and gene expression of retinal pro-angiogenic factors was measured by qRT-PCR.
  
  
  RESULTS
  Retinas from ROP GPx1 KO mice had a significantly larger central avascular area compared to those from ROP WT mice (P < 0.001), indicative of a more severe vaso-obliteration. In ROP GPx1 KO mice, retinas also displayed increased preretinal neovascularization (P = 0.05) with a concurrent increase in the expression of vascular endothelial growth factor (P < 0.05) compared to values in ROP WT mice. Elevated oxidative stress was observed in ROP GPx1 KO retinas as evidenced by increased nitrotyrosine immunolabeling (P < 0.01) and superoxide (P < 0.05) in vessels compared to ROP WT retinas. In contrast to these findings of exacerbated retinal vascular injury in GPx1 KO mice, Müller cell gliosis and microglial density were similar in ROP GPx1 KO and ROP WT mice.
  
  
  CONCLUSIONS
  GPx1, an important antioxidant enzyme of the premature retina, afforded protection against oxidative stress and oxidative injury in ROP. Lack of GPx1 was associated with increased oxidative stress, an increase in retinal avascular area, upregulation of retinal VEGF, and increased neovascularization in a mouse model of ROP.
authors.affiliation: Oxidative Stress Group, Division of Diabetic Complications, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Sih Min
authors.initials: SM
authors.lastname: Tan
authors.forename: Nada
authors.initials: N
authors.lastname: Stefanovic
authors.forename: Genevieve
authors.initials: G
authors.lastname: Tan
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Wilkinson-Berka
authors.forename: Judy B
authors.initials: JB
authors.lastname: de Haan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D005979:Glutathione Peroxidase / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D012160:Retina / Q000201:enzymology* / Q000473:pathology; D012164:Retinal Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000975:Antioxidants; D012313:RNA; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse