A new mouse model of dry eye disease: oxidative stress affects functional decline in the lacrimal gland

Cornea. 2012 Nov;31 Suppl 1:S63-7. doi: 10.1097/ICO.0b013e31826a5de1.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Dry Eye Syndromes / physiopathology*
  • Lacrimal Apparatus / physiopathology*
  • Mice
  • Mice, Transgenic
  • Mitochondria / metabolism*
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Tears / physiology

Substances

  • Reactive Oxygen Species