title: A new mouse model of dry eye disease:  oxidative stress affects functional decline in the lacrimal gland.
abstract: OBJECTIVE
  Oxidative damage and inflammation are proposed to be involved in the age-related functional decline of lacrimal glands. The molecular mechanism(s) of how oxidative stress affects the secretory function of lacrimal glands was investigated because this is currently unclear.
  
  
  METHODS
  We used a novel mev-1 conditional transgenic mouse model (Tet-mev-1) with a modified tetracycline system. The mev-1 gene encodes the cytochrome b560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria.
  
  
  RESULTS
  Expression of the mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in aqueous secretory function. Tear volume in Tet-mev-1 mice was lower than in wild-type mice, and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice.
  
  
  CONCLUSIONS
  This new model provides evidence that mitochondria-induced oxidative damage in the lacrimal gland induces lacrimal dysfunction, resulting in dry eye disease. Our findings strongly suggest that oxidative stress can be a causative factor in the development of dry eye disease.
authors.affiliation: Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan. hmpgx653@yahoo.co.jp
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uchino
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawakita
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ishii
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ishii
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tsubota
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000503:physiopathology*; D007765:Lacrimal Apparatus / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013666:Tears / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species