title: Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.
abstract: OBJECTIVE
  The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1-/-) mouse.
  
  
  METHODS
  Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1-/- male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild-type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed.
  
  
  RESULTS
  Corneal vital staining scores in the Sod1-/- mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1-/- mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1-/- mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1-/- mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1-/- mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1-/- mice.
  
  
  CONCLUSIONS
  Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1-/- mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.
authors.forename: Osama M A
authors.initials: OM
authors.lastname: Ibrahim
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan; Tokyo Dental College, Department of Ophthalmology, Chiba, Japan.
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Tokyo Dental College, Department of Ophthalmology, Chiba, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Igarashi
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.
authors.forename: Tais Hitomi
authors.initials: TH
authors.lastname: Wakamatsu
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, 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: Tokyo Dental College, Department of Ophthalmology, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimazaki
authors.affiliation: Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D004249:DNA Damage; D015352:Dry Eye Syndromes / Q000209:etiology / Q000503:physiopathology; D019573:Epithelium, Corneal / Q000473:pathology; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008537:Meibomian Glands / Q000201:enzymology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000172:deficiency*; D000072105:Superoxide Dismutase-1; D013666:Tears / Q000737:chemistry / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1