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Yuichi Uchino, Tetsuya Kawakita, Masaki Miyazawa, Takamasa Ishii, Hiromi Onouchi, Kayo Yasuda, Yoko Ogawa, Shigeto Shimmura, Naoaki Ishii, Kazuo Tsubota; The Role Of Intracellular Oxidative Stress In The Mechanism Of The Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3750.
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Tet-mev-1 mice has a mutation in SDHC subunit constituting mitochondrial complex II caused superoxide anion (O2-) overproduction using our unique tetracycline (Tet On/Off) system. Tet-mev-1 mice showed more inflammation in lacrimal gland and lower tear volume than wild type (WT), and we reported Tet-mev-1 mice as a dry eye disease model. The purpose of this study was to analyze the inflammatory cytokine expression level and the autoimmune reaction in the lacrimal gland of the Tet-mev-1 mice.
The extraction of the RNA in the lacrimal gland and the sampling of blood serum were performed on Tet-mev-1 mice (n=5) and WT mice (n=5) at aged of 3 months. The expression level of the inflammatory cytokine in the lacrimal gland was analyzed by real-time PCR. For serum, anti-SSA/Ro antibody titers was measured by ELISA kit, and the serum was also used for the immunity tissue staining as primary antibody in merotomy of WT to analyze the presence of autoantibody.
Inflammatory cytokine (ex. TNFα) mRNA expression level of the lacrimal gland in Tet-mev-1 mice was higher than WT. There is no significant difference about anti-SSA/Ro antibody titers of serum in the both groups. The serum of Tet-mev-1 mouse had a little stainning by merotomy of WT, but Tet-mev-1 mouse serum did not have the reactivity with the autoantibody.
Tet-mev-1 mouse had the invasion of inflammatory cells with the increase of the inflammatory cytokines in lacrimal gland, in result, which induced secretory dysfunction of lacrimal gland. In the mechanism, autoantibody was not found in Tet-mev-1 mouse serum. These findings suggested that oxidative stress could be a causative factor for the development of non-autoimmune dry eye disease.
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