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Yukihisa Takada, Osamu Yamanaka, Yuka Okada, Takayoshi Sumioka, Tadahiko Tamura, Shizuya Saika; Effects of a Rho kinase inhibitor on epithelial wound healing of a mouse cornea. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3225. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported that adding Ripasudil hydrochloride hydrate (a Rho kinase inhibitor, RIPASUDIL) to the medium accelerated proliferation and migration of corneal epithelial cells in vitro and ex vivo (2018 ARVO). We here examined the effects of RIPASUDIL on expression of E-cadherin in corneal epithelium of an organ-cultured mouse eye and on in vivo epithelial wound healing in mice.
(1) The eyeballs of wild type mice were cultured for 24 hrs in the presence or absence of RIPASUDIL (10μM, KOWA Co. Ltd.). Expression of cell-cell adhesion molecule (E-cadherin) was evaluated using immunocytochemistry. (2) We made a 2.0 mm diameter circular corneal epithelial defect in wild type mice by surgical blade. We then evaluated epithelial recover with (n = 6) or without topical 0.4% RIPASUDIL (every 6 hr-administration, n = 7). The wound healing rate was determined by the % remaining epithelial cell defect by using Image J. Data were statistically analyzed by Mann-Whitney U test.
(1) RIPASUDIL changed immune-localization, but not expression level, of E-cadherin; E-cadherin expression was observed at intercellular junction densely in control, but RIPASUDIL group showed discontinuous expression around cell junction. Western blot showed no difference of total E-cadherin protein in both groups. (2) At 6 hours, topical RIPASUDIL significantly promoted wound healing of the corneal epithelial defect. At 24 hours, the wound was totally resurfaced in both control and treatment groups.
RIPASUDIL promotes wound healing of corneal epithelium in mice relatively early phase of wound healing in association with alteration of cell junction machinery.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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