Effects of oxidative stress on the conjunctiva in Cu, Znsuperoxide dismutase-1 (Sod1)-knockout mice

Takashi Kojima, Murat Dogru, Osama M A Ibrahim, Tais Hitomi Wakamatsu, Masataka Ito, Ayako Igarashi, Takaaki Inaba, Takahiko Shimizu, Takuji Shirasawa, Jun Shimazaki, Kazuo Tsubota

Research output: Contribution to journalArticle

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Abstract

PURPOSE. A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1-/-mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression.METHODS. Fifty-week-old C57/B6 wild-type (WT) and Sod1-/-mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with anti-Muc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-20-deoxyguanosine anti-bodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR.RESULTS. The mean goblet cell density in the aged Sod1-/-mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1-/- mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1-/-mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1-/-mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1-/-mice was also significantly lower than the aged WT mice.CONCLUSIONS. Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1-/- mice.

Original languageEnglish
Pages (from-to)8382-8391
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number13
DOIs
Publication statusPublished - 2015 Dec 1

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Conjunctiva
Knockout Mice
Oxidative Stress
Goblet Cells
Mucins
Staining and Labeling
Tears
Messenger RNA
Epithelium
Cell Count
Phenotype
Periodic Acid
Deoxyguanosine
Superoxide Dismutase-1
Real-Time Polymerase Chain Reaction
Immunohistochemistry

Keywords

  • Conjunctiva
  • Mucin
  • Oxidative stress
  • Sod1

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Effects of oxidative stress on the conjunctiva in Cu, Znsuperoxide dismutase-1 (Sod1)-knockout mice. / Kojima, Takashi; Dogru, Murat; Ibrahim, Osama M A; Wakamatsu, Tais Hitomi; Ito, Masataka; Igarashi, Ayako; Inaba, Takaaki; Shimizu, Takahiko; Shirasawa, Takuji; Shimazaki, Jun; Tsubota, Kazuo.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 13, 01.12.2015, p. 8382-8391.

Research output: Contribution to journalArticle

Kojima, T, Dogru, M, Ibrahim, OMA, Wakamatsu, TH, Ito, M, Igarashi, A, Inaba, T, Shimizu, T, Shirasawa, T, Shimazaki, J & Tsubota, K 2015, 'Effects of oxidative stress on the conjunctiva in Cu, Znsuperoxide dismutase-1 (Sod1)-knockout mice', Investigative Ophthalmology and Visual Science, vol. 56, no. 13, pp. 8382-8391. https://doi.org/10.1167/iovs.15-18295
Kojima, Takashi ; Dogru, Murat ; Ibrahim, Osama M A ; Wakamatsu, Tais Hitomi ; Ito, Masataka ; Igarashi, Ayako ; Inaba, Takaaki ; Shimizu, Takahiko ; Shirasawa, Takuji ; Shimazaki, Jun ; Tsubota, Kazuo. / Effects of oxidative stress on the conjunctiva in Cu, Znsuperoxide dismutase-1 (Sod1)-knockout mice. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 13. pp. 8382-8391.
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abstract = "PURPOSE. A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1-/-mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression.METHODS. Fifty-week-old C57/B6 wild-type (WT) and Sod1-/-mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with anti-Muc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-20-deoxyguanosine anti-bodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR.RESULTS. The mean goblet cell density in the aged Sod1-/-mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1-/- mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1-/-mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1-/-mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1-/-mice was also significantly lower than the aged WT mice.CONCLUSIONS. Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1-/- mice.",
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T1 - Effects of oxidative stress on the conjunctiva in Cu, Znsuperoxide dismutase-1 (Sod1)-knockout mice

AU - Kojima, Takashi

AU - Dogru, Murat

AU - Ibrahim, Osama M A

AU - Wakamatsu, Tais Hitomi

AU - Ito, Masataka

AU - Igarashi, Ayako

AU - Inaba, Takaaki

AU - Shimizu, Takahiko

AU - Shirasawa, Takuji

AU - Shimazaki, Jun

AU - Tsubota, Kazuo

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N2 - PURPOSE. A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1-/-mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression.METHODS. Fifty-week-old C57/B6 wild-type (WT) and Sod1-/-mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with anti-Muc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-20-deoxyguanosine anti-bodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR.RESULTS. The mean goblet cell density in the aged Sod1-/-mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1-/- mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1-/-mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1-/-mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1-/-mice was also significantly lower than the aged WT mice.CONCLUSIONS. Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1-/- mice.

AB - PURPOSE. A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1-/-mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression.METHODS. Fifty-week-old C57/B6 wild-type (WT) and Sod1-/-mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with anti-Muc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-20-deoxyguanosine anti-bodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR.RESULTS. The mean goblet cell density in the aged Sod1-/-mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1-/- mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1-/-mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1-/-mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1-/-mice was also significantly lower than the aged WT mice.CONCLUSIONS. Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1-/- mice.

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KW - Mucin

KW - Oxidative stress

KW - Sod1

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