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Y. Uchino, M. Miyazawa, M. Tanigawa, H. Onouchi, K. Yasuda, M. Kirinashizawa, N. Ishii, K. Tsubota; A New Mouse Model of Dry Eye Disease (Tet-mev-1 Mice): Oxidative Stress Affect Functional Decline in Lacrimal Gland. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3646.
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A mutation in SDHC subunit constituting mitochondrial complex II caused superoxide anion overproduction leading to excessive apoptosis, precocious aging or tumorigenesis in both nematode C. elegans mev-1 and mouse fibroblast cells SDHC E69. We have constructed conditional transgenic mice (Tet-mev-1) with the mutation in SDHC gene coding SDHC V69E mutation using our unique tetracycline (Tet On/Off) system. Tet-mev-1 homozygous (Tet-mev-1 37 Tg/Tg) mice increased O2- levels in the mitochondria and apoptosis induction of several tissues. The purpose of our study was to determine the histopathological and biochemical alternations in the lacrimal gland of Tet-mev-1 mice as a dry eye model.
Tear function test (tear quantity measured with 0.5 µl microcapillary) were performed on Tet-mev-1 mice (n=6) aged 3 months and wild type mice (n=6).At 3 months age, these mice are sacrificed and the lacrimal glands were collected for measurement of superoxide anion (O2-) as the result of electron leakage from complex II and for histopathology analyses.As histopathological analyses, Haematoxylin and Eosin, Periodic Acid Schiff stainings were performed. The study was conducted in compliance with the ARVO statement for the use of animals in Ophthalmic and Visual Research.
Tear quantity values in Tet-mev-1 mice were lower compared to the wild type mice detected by the measurement with 0.5µl microcapillary. The lacrimal gland of Tet-mev-1 mice overproduced superoxide anion (O2-) compared to the wild type mice. Histopathological analysis showed the hallmarks of lacrimal gland inflammation by presence of intense mononuclear leukocytic infiltration and decrease of acinar cell by the destruction in the lacrimal gland of Tet-mev-1 mice.
Tet-mev-1 mice revealed decreased tear production with the morphological changes. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.
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