A new mouse model of dry eye disease: Oxidative stress affects functional decline in the Lacrimal Gland

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.