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Hiroshi Tanaka, Tomonori Nakayama, Michiko Tsukamoto, Takahiro Nakamura, Akihide Watanabe, Chie Sotozono, Shigeru Kinoshita; Rebamipide attenuates lacrimal duct epithelial cell damage in a rabbit model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):109.
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Inflammation and fibrosis due to aging of lacrimal duct epithelium are thought to be involved in the pathology of idiopathic nasolacrimal-duct obstruction. Interleukin 6 (IL-6) is reportedly involved in the pathology of congenital nasolacrimal duct obstruction. Rebamipide is marketed in Japan as an ophthalmic suspension for the treatment of dry eye. We previously reported that rebamipide has a protective effect against cultured corneal epithelial cell damage. In this study, we investigated the barrier function and protective effect of rebamipide on rabbit lacrimal duct epithelial cells.
As an in vitro experiment, a rabbit lacrimal duct was sampled and epithelial cells were collected with Pronase and cultured on the dish. The cells were subcultured on 24-well Transwell™ plates (Corning Inc., Corning, NY) and transepithelial electrical resistance (TER) was measured over 72 hours with or without IL-6 (0.5ng/ml) or rebamipide (2mM) (n=2 each). As an in vivo experiment, a rabbit lacrimal duct epithelial cell damage model was created by injecting 250µl of 1% benzalkonium chloride (BAC) into the rabbit’s lacrimal duct once daily for 3 consecutive days and 250μl of 2% rebamipide ophthalmic solution or the base being injected (n=3 each) at the same time. The extent of mucosal damage was compared by histological examination.
In the in vitro experiment, the TER ratio (TER after the 72-hour experiment/TER pre experiment) was 1.00±0.010, 1.51±0.004, 0.78±0.046, and 0.96±0.058 [IL-6 (ng/ml)- rebamipide (mM); 0-0, 0-2, 0.5-0, and 0.5-2]. In the in vivo experiment, shedding of lacrimal duct epithelial cells was observed by 1% BAC injection in the histological examination as a lacrimal duct epithelial cell damage model. In these models, the shedding of lacrimal-duct epithelial cells was markedly observed in the base injection group and a marked decrease in epithelial cell loss was confirmed in the rebamipide injected group.
Rebamipide restores the barrier function of lacrimal duct epithelial cells and has a protective effect against inflammation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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