Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice

Sihmin Tan, Nada Stefanovic, Genevieve May Lee Tan, Jennifer Wilkinson-Berka, Judy B de Haan

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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, Muller 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. Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc
Original languageEnglish
Pages (from-to)555 - 562
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013

Cite this

@article{48e591e9be0a41b1a5b7ae26ab760384,
title = "Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice",
abstract = "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, Muller 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. Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc",
author = "Sihmin Tan and Nada Stefanovic and Tan, {Genevieve May Lee} and Jennifer Wilkinson-Berka and {de Haan}, {Judy B}",
year = "2013",
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doi = "10.1167/iovs.12-10685",
language = "English",
volume = "54",
pages = "555 -- 562",
journal = "Investigative Ophthalmology and Visual Science",
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Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice. / Tan, Sihmin; Stefanovic, Nada; Tan, Genevieve May Lee; Wilkinson-Berka, Jennifer; de Haan, Judy B.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 1, 01.01.2013, p. 555 - 562.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Lack of the antioxidant glutathione peroxidase-1 (GPx1) exacerbates retinopathy of prematurity in mice

AU - Tan, Sihmin

AU - Stefanovic, Nada

AU - Tan, Genevieve May Lee

AU - Wilkinson-Berka, Jennifer

AU - de Haan, Judy B

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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, Muller 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. Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc

AB - 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, Muller 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. Copyright 2013 The Association for Research in Vision and Ophthalmology, Inc

UR - http://www.ncbi.nlm.nih.gov/pubmed/23287791

U2 - 10.1167/iovs.12-10685

DO - 10.1167/iovs.12-10685

M3 - Article

VL - 54

SP - 555

EP - 562

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 1552-5783

IS - 1

ER -