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T. Kojima, O. M. A. Ibrahim, T. H. Wakamatsu, T. Shimizu, M. Dogru, K. Tsubota; Effects of Oxidative Stress on Conjunctiva/Ocular Surface and Tear Functions in Sod1 (-/-) Mouse. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1918.
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© ARVO (1962-2015); The Authors (2016-present)
Healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used the Sod1(-/-) mice deficient in Cu, Zn - superoxide dismutase 1 (SOD1) and investigated the effect of oxidative stress on the conjunctival phenotype/ocular surface health and tear functions.
Fifty weeks old C57/B6 wild type mice (wt) and Sod1(-/-) mice were used for evaluations of the tear film break-up time (BUT), fluorescein staining of the cornea, and the periodic acid Schiff (PAS) staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry staining with anti-MUC5AC and anti-4-hydroxy-2-nonenal (4HNE) antibodies were also performed.
The mean BUT value was 2.8±1.5s and 3.8±0.8s in the Sod1(-/-) and wt mice, respectively (p< 0.05). The respective corneal fluorescein staining score was 5.0±1.6 and 3.3±1.0 points, respectively (p< 0.05). The conjunctiva of Sod1(-/-) mice showed marked thickening of conjunctival epithelium and keratinization. The goblet cell density in the wt mice was 58.9±24.7 compared to 4.8±5.1 cells/ fornix in the Sod1(-/-) mice, respectively (p< 0.05). The number of cells positively stained with MUC5AC were significantly lower in the Sod1(-/-) mice (2.6±2.7 cells/fornix) compared to the wt mice (12.3±4.9 cells/fornix) (p < 0.05). Conjunctival epithelium in Sod1(-/-) mice displayed marked staining with 4HNE antibodies.
Marked tear instability with decreased MUC5AC secreting goblet cells, corneal epithelial damage and increased lipid oxidation were the prominent features of the ocular surface disease in the Sod1(-/-) mice. Elevated conjunctival oxidative stress status appears to affect the conjunctival mucin secretions and the epithelial phenotype. Sod1(-/-) mice may serve as a good model for mucin deficient dry eye disease.
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