TY - JOUR
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
N1 - Publisher Copyright:
© 2015 The Association for Research in Vision and Ophthalmology, Inc.
PY - 2015/12/1
Y1 - 2015/12/1
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.
KW - Conjunctiva
KW - Mucin
KW - Oxidative stress
KW - Sod1
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U2 - 10.1167/iovs.15-18295
DO - 10.1167/iovs.15-18295
M3 - Article
C2 - 26747769
AN - SCOPUS:84952934168
SN - 0146-0404
VL - 56
SP - 8382
EP - 8391
JO - Investigative Ophthalmology
JF - Investigative Ophthalmology
IS - 13
ER -