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Lack of the Antioxidant Glutathione Peroxidase-1 (GPx1) Exacerbates Retinopathy of Prematurity in Mice.
MedLine Citation:
PMID:  23287791     Owner:  NLM     Status:  Publisher    
PURPOSE: 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 wildtype (WT) and GPx1 knockout (KO) mice by exposing neonatal mice to 75% oxygen from postnatal days 7 to 11, followed by one week of room air. Structural effects of ROP were evaluated by retinal histology and gene expressions of retinal pro-angiogenic factors were measured by qRT-PCR. RESULTS: Retinas from ROP GPx1 KO mice had a significantly larger central avascular area compared to ROP WT mice (P<0.001) indicative of a more severe vaso-obliteration. In ROP GPx1 KO mice, retinas also displayed increased pre-retinal neovascularization (P=0.05) with a concurrent increase in the expression of vascular endothelial growth factor (P<0.05), compared to ROP WT mice. Elevated oxidative stress was observed in ROP GPx1 KO retinas as evidenced by the increased ntirotyrosine immunolabelling (P<0.01) and superoxide (P<0.05) in vessels compared to ROP WT. 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.
Sih Min Tan; Nada Stefanovic; Genevieve Tan; Jennifer L Wilkinson-Berka; Judy B de Haan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-3
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  -     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Oxidative Stress Group, Division of Diabetic Complications, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
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