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Cornea:
doi: 10.1097/ICO.0b013e31826a5de1
Article

A New Mouse Model of Dry Eye Disease: Oxidative Stress Affects Functional Decline in the Lacrimal Gland

Uchino, Yuichi MD*; Kawakita, Tetsuya MD*; Ishii, Takamasa PhD; Ishii, Naoaki PhD; Tsubota, Kazuo MD*

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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.

© 2012 Lippincott Williams & Wilkins, Inc.

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