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Ryoichi Sawazaki, Tomoaki Ishihara, Tohru Mizushima; Ameliorative effect of an approved medicine on corneal surface damage in a rat model of dry eye. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1970.
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Dry eye syndrome (DES) is characterized by an increase in tear osmolarity due to a decrease in both the volume and quality of tears, which in turn induces chronic irritation of the ocular surface. Induction of the expression and nuclear localization of an osmoprotective transcription factor (nuclear factor of activated T-cells 5 (NFAT5)) plays an important role in providing protection against hyperosmotic tears. Compounds that protect ocular epithelial cells against hyperosmotic tears would make good candidates as DES drugs, though such drugs have not been identified at present. In this study, we have screened medicines already in clinical use with a view of finding compounds that protect cultured human corneal epithelial cells against hyperosmolarity-induced cell damage. The in vitro experiments on cultured cells were confirmed in vivo on a rat model for DES.
Viable cell number was determined by the MTT method and cellular NFAT5 level was measured by immunoblotting. The rat model for DES was developed by removal of the lacrimal glands, with an assessment of corneal surface damage based on levels of fluorescein staining and epithelial apoptosis.
We found an approved medicine A during the screening procedure. This approved medicine was able to suppress hyperosmolarity-induced apoptosis and cell growth arrest. On the other hands, some medicines categorized in the same type of medicine as an approved medicine A did not exert such a protective action. Treatment of cells with this approved medicine stimulated both the nuclear localization and expression of NFAT5 under hyperosmotic conditions. In the rat model for DES, topical administration of this approved medicine to eyes reduced corneal surface damage without affecting the volume of tear fluid.
This approved medicine appears to protect cells against hyperosmolarity-induced cell damage. NFAT5 would play an important role in this protective action. The findings reported here may also indicate that the topical administration of this approved medicine to eyes may be therapeutically beneficial for DES patients.
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