title: Effects of Oxidative Stress on the Conjunctiva in Cu, Zn-Superoxide Dismutase-1 (Sod1)-Knockout Mice.
abstract: OBJECTIVE
  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-2'-deoxyguanosine antibodies 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.
authors.affiliation: Department of Ophthalmology Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Ophthalmology Keio University School of Medicine, Tokyo, Japan 2Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.affiliation: Department of Ophthalmology Keio University School of Medicine, Tokyo, Japan.
authors.forename: Osama M A
authors.initials: OM
authors.lastname: Ibrahim
authors.affiliation: Department of Ophthalmology, São Paulo University School of Medicine, São Paulo, Brazil.
authors.forename: Tais Hitomi
authors.initials: TH
authors.lastname: Wakamatsu
authors.affiliation: Department of Developmental Anatomy and Regenerative Biology, National Defense Medical College, Saitama, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Igarashi
authors.affiliation: Department of Ophthalmology Keio University School of Medicine, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Inaba
authors.affiliation: Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Aging Control Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.affiliation: Department of Ophthalmology, Tokyo Dental College, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.affiliation: Department of Ophthalmology Keio University School of Medicine, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D003228:Conjunctiva / Q000166:cytology / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000096:biosynthesis; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013666:Tears / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D009077:Mucins; D003300:Copper; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D015032:Zinc