Retinal Light Damage: Structural and Functional Effects of the Antioxidant Glutathione Peroxidase-1

Gosbell, Andrew; Stefanovic, Nada; Scurr, Lyndee L.; Pete, Josefa; Kola, Ismail; Favilla, Ian

doi:10.1167/iovs.05-0962

Cited by 32 publications

(29 citation statements)

References 57 publications

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“…The approximately 20% of residual GPx1 expression in the GPx1 KO retinas was most likely due to background and/or nonspecific primer amplification as previously described in the same animal model. 24 There was a significant increase of GPx1 gene expression in the ROP WT retina compared to the sham WT retina, which was not observed in GPx1 KO retinas. In contrast, GPx2, GPx3, and GPx4 gene expression was not altered across all experimental groups (see Supplementary Material and Supplementary Figs.…”

Section: Retinal Antioxidant Gene Expressionmentioning

confidence: 83%

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Lack of the Antioxidant Glutathione Peroxidase-1 (GPx1) Exacerbates Retinopathy of Prematurity in Mice

Tan

Stefanovic

Tan

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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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 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 ¼ 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. (Invest Ophthalmol Vis Sci. 2013;54:555-562)

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Section: Retinal Antioxidant Gene Expressionmentioning

confidence: 83%

“…15 GPx has previously been reported to play important roles in protecting the retina from phototoxicity 24,30 and cataract formation. 31 The GPx enzyme family consists of four selenium-dependent isoforms, GPx1, GPx2, GPx3, and GPx4.…”

Section: Discussionmentioning

confidence: 99%

Lack of the Antioxidant Glutathione Peroxidase-1 (GPx1) Exacerbates Retinopathy of Prematurity in Mice

Tan

Stefanovic

Tan

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Knock-out mice of antioxidant enzymes created to date include SOD1 Ϫ/Ϫ mice (12) and GPx1 Ϫ/Ϫ mice (11). Both SOD1 and GPx1 localize in the cytosol, not mitochondria.…”

Section: Discussionmentioning

confidence: 99%

“…However, their essentiality has remained unclear. Although several studies have reported the knock-out mice of antioxidant enzymes, they have not shown severe photoreceptor cell abnormality or degeneration (11,12). This is probably because multiple antioxidant enzymes share target substrates; thus compensating for each other.…”

mentioning

confidence: 99%

Glutathione Peroxidase 4 Is Required for Maturation of Photoreceptor Cells

Ueta

Inoue

Furukawa³

et al. 2012

Journal of Biological Chemistry

108

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Background:The essentiality of an antioxidant enzyme for the development and maturation of photoreceptor cells has remained unclear. Results: While GPx4-abrogated photoreceptor cells develop and differentiate into rod and cone cells, their outer segments are structurally disorganized and they undergo rapid apoptosis in vivo. Conclusion: GPx4 is essential for the maturation of photoreceptor cells. Significance: A novel role of an antioxidant enzyme for photoreceptor cells is disclosed in this study.

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“…Retinal damage due to excessive exposure to solar radiation or intense artificial sources of light has been demonstrated in a number of studies (Kirkness 1986;Gosbell, Stefanovic et al 2006). However, while several epidemiologic studies support the role of chronic exposure to sunlight in the development of AMD (Taylor, West et al 1992;Delcourt, Carriere et al 2001), the acceptance that chronic exposure to less intense light sources plays a role in retinal injury is still controversial.…”

Section: Motivation and Purposementioning

confidence: 99%

Distribution of Light in the Human Retina under Natural Viewing Conditions

Gibert¹

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Retinal Light Damage: Structural and Functional Effects of the Antioxidant Glutathione Peroxidase-1

Cited by 32 publications

References 57 publications

Lack of the Antioxidant Glutathione Peroxidase-1 (GPx1) Exacerbates Retinopathy of Prematurity in Mice

Lack of the Antioxidant Glutathione Peroxidase-1 (GPx1) Exacerbates Retinopathy of Prematurity in Mice

Glutathione Peroxidase 4 Is Required for Maturation of Photoreceptor Cells

Distribution of Light in the Human Retina under Natural Viewing Conditions

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