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Michiko Tsukamoto, Hiroshi Tanaka, Tomonori Nakayama, Takahiro Nakamura, Akihide Watanabe, Chie Sotozono, Shigeru Kinoshita; Rebamipide promotes lacrimal-duct epithelial cell survival via protecting the barrier function. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6242.
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Inflammation and fibrosis due to the aging of lacrimal-duct epithelium are thought to be involved in the pathology of idiopathic nasolacrimal-duct obstruction (NDO). It was recently reported that interleukin 6 (IL-6) is involvedin the pathology of NDO. Thus, the suppression of inflammation is considered keyto new treatments. We previously reported that rebamipide ophthalmic suspension, marketed in Japan for the treatment of dry eye, has a protective effect against cultured corneal epithelial cell damage. Here weinvestigated the effect of rebamipide on lacrimal-duct epithelial cells (LDECs), both in vitroand in vivo.
LDEC barrier functionwas examined in vitro by measurement of transepithelial electrical resistance (TER) at 0-, 24-, and 72-hours post stimulation with or without IL-6 and/orrebamipide; GroupA(placebo vehicle), GroupB[IL-6 (0.5ng/ml)], and GroupC[IL-6 (0.5ng/ml)and rebamipide(2mM)]. For thein vivoexamination, 1% benzalkonium chloride (BAC) was injected into rabbit lacrimal ducts to create a lacrimal-duct injury model, followed by 2% rebamipide or the placebo vehicle alonebeing applied for 3 days. The anatomical and functional changes of LDECs in vivo were then evaluated by histological, immunohistochemical, and electron-microscopy analysis.
In the in vitroexamination, no significant difference was observed among the 3 groups at 0- and 24-hours post stimulation. However, at 72-hours post stimulation, a significant decrease in TER was observed in Group B (IL-6 alone) compared to Group A (placebo vehicle) (p<0.05) and Group C (IL-6 and rebamipide) (p<0.01).In the in vivo examination, rebamipide was found to attenuatethe disturbance of tissue construction, such as the shedding or enucleation of epithelial cells and the shortening of microvilli on the surface of epithelial cells, as well as the infiltration of neutrophils under the basement membrane. Immunohistochemical analysis revealed that tight junction protein zonula occludens (ZO)-1, claudin (CLDN)-1, and CLDN-7 were also disrupted in the BAC and the placebo vehicle injected groups, whereas those expressions were expressed in the group injected with BAC and rebamipide.
Rebamipide protected LDECs via an anti-inflammatory effect and preserved the barrier function, thus suggesting that rebamipide may prevent the death of LDECs due to inflammation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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