The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice

Takeshi Ohguchi, Takashi Kojima, Osama M. Ibrahim, Taeko Nagata, Takahiko Shimizu, Takuji Shirasawa, Tetsuya Kawakita, Yoshiyuki Satake, Kazuo Tsubota, Jun Shimazaki, Susumu Ishida

Research output: Contribution to journalArticle

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Abstract

Purpose. To investigate the efficacy of 2% rebamipide ophthalmic solution on the tear functions and ocular surface status of the superoxide dismutase-1(Sod1-/-) mice. Methods. Two percent Rebamipide ophthalmic solution was applied to 40-week-old male Sod1-/- and wild-type (WT) mice four times a day for 2 weeks. We examined the cytokine concentrations in the tear fluid (by CytoBead assay), tear film break-up time, amount of tear production, and expressions of mucins 1, 4, and 5AC, by RT-PCR. We also performed vital staining of the ocular surface, PAS staining for muc5AC, and immunohistochemical stainings for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), in the conjunctiva to compare the Results before and after rebamipide instillations. Results. The tear functions and ocular surface epithelial damage scores were significantly worse in the Sod1-/- than in the WT mice. Application of 2% rebamipide for 2 weeks significantly improved the tear film break-up time, the amount of tear production, and the corneal epithelial damage scores, which also significantly increased the conjunctival goblet cell density and muc5 mRNA expression, in the Sod1-/- mice. The mean IL-6, IL-17, TNF-α, and IFN-γ levels in the tear fluid were reduced significantly along with a significant decrease in the density of cells positive for 4-HNE and 8-OHdG in the conjunctiva. Conclusions. Two percent Rebamipide ophthalmic solution significantly improved the tear stability and corneal epithelial damage, and enhanced the expression of muc5 mRNA on the ocular surface. We also observed anti-inflammatory effects in the tear film together with antioxidative effects in the conjunctiva, suggesting the efficacy of rebamipide in age-related dry eye disease attributable to SOD1 knockout.

Original languageEnglish
Pages (from-to)7793-7802
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number12
DOIs
Publication statusPublished - 2013 Nov 21

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Ophthalmic Solutions
Tears
Knockout Mice
Conjunctiva
Staining and Labeling
Mucin 5AC
Mucin-4
Cell Count
rebamipide
Superoxide Dismutase-1
Mucin-1
Messenger RNA
Goblet Cells
Interleukin-17
Eye Diseases
Interleukin-6
Anti-Inflammatory Agents
Cytokines
Polymerase Chain Reaction

Keywords

  • Dry eyes
  • Inflammation
  • Secretagogue

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice. / Ohguchi, Takeshi; Kojima, Takashi; Ibrahim, Osama M.; Nagata, Taeko; Shimizu, Takahiko; Shirasawa, Takuji; Kawakita, Tetsuya; Satake, Yoshiyuki; Tsubota, Kazuo; Shimazaki, Jun; Ishida, Susumu.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 12, 21.11.2013, p. 7793-7802.

Research output: Contribution to journalArticle

Ohguchi, T, Kojima, T, Ibrahim, OM, Nagata, T, Shimizu, T, Shirasawa, T, Kawakita, T, Satake, Y, Tsubota, K, Shimazaki, J & Ishida, S 2013, 'The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice', Investigative Ophthalmology and Visual Science, vol. 54, no. 12, pp. 7793-7802. https://doi.org/10.1167/iovs.13-13128
Ohguchi, Takeshi ; Kojima, Takashi ; Ibrahim, Osama M. ; Nagata, Taeko ; Shimizu, Takahiko ; Shirasawa, Takuji ; Kawakita, Tetsuya ; Satake, Yoshiyuki ; Tsubota, Kazuo ; Shimazaki, Jun ; Ishida, Susumu. / The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 12. pp. 7793-7802.
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abstract = "Purpose. To investigate the efficacy of 2{\%} rebamipide ophthalmic solution on the tear functions and ocular surface status of the superoxide dismutase-1(Sod1-/-) mice. Methods. Two percent Rebamipide ophthalmic solution was applied to 40-week-old male Sod1-/- and wild-type (WT) mice four times a day for 2 weeks. We examined the cytokine concentrations in the tear fluid (by CytoBead assay), tear film break-up time, amount of tear production, and expressions of mucins 1, 4, and 5AC, by RT-PCR. We also performed vital staining of the ocular surface, PAS staining for muc5AC, and immunohistochemical stainings for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), in the conjunctiva to compare the Results before and after rebamipide instillations. Results. The tear functions and ocular surface epithelial damage scores were significantly worse in the Sod1-/- than in the WT mice. Application of 2{\%} rebamipide for 2 weeks significantly improved the tear film break-up time, the amount of tear production, and the corneal epithelial damage scores, which also significantly increased the conjunctival goblet cell density and muc5 mRNA expression, in the Sod1-/- mice. The mean IL-6, IL-17, TNF-α, and IFN-γ levels in the tear fluid were reduced significantly along with a significant decrease in the density of cells positive for 4-HNE and 8-OHdG in the conjunctiva. Conclusions. Two percent Rebamipide ophthalmic solution significantly improved the tear stability and corneal epithelial damage, and enhanced the expression of muc5 mRNA on the ocular surface. We also observed anti-inflammatory effects in the tear film together with antioxidative effects in the conjunctiva, suggesting the efficacy of rebamipide in age-related dry eye disease attributable to SOD1 knockout.",
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AU - Ibrahim, Osama M.

AU - Nagata, Taeko

AU - Shimizu, Takahiko

AU - Shirasawa, Takuji

AU - Kawakita, Tetsuya

AU - Satake, Yoshiyuki

AU - Tsubota, Kazuo

AU - Shimazaki, Jun

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N2 - Purpose. To investigate the efficacy of 2% rebamipide ophthalmic solution on the tear functions and ocular surface status of the superoxide dismutase-1(Sod1-/-) mice. Methods. Two percent Rebamipide ophthalmic solution was applied to 40-week-old male Sod1-/- and wild-type (WT) mice four times a day for 2 weeks. We examined the cytokine concentrations in the tear fluid (by CytoBead assay), tear film break-up time, amount of tear production, and expressions of mucins 1, 4, and 5AC, by RT-PCR. We also performed vital staining of the ocular surface, PAS staining for muc5AC, and immunohistochemical stainings for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), in the conjunctiva to compare the Results before and after rebamipide instillations. Results. The tear functions and ocular surface epithelial damage scores were significantly worse in the Sod1-/- than in the WT mice. Application of 2% rebamipide for 2 weeks significantly improved the tear film break-up time, the amount of tear production, and the corneal epithelial damage scores, which also significantly increased the conjunctival goblet cell density and muc5 mRNA expression, in the Sod1-/- mice. The mean IL-6, IL-17, TNF-α, and IFN-γ levels in the tear fluid were reduced significantly along with a significant decrease in the density of cells positive for 4-HNE and 8-OHdG in the conjunctiva. Conclusions. Two percent Rebamipide ophthalmic solution significantly improved the tear stability and corneal epithelial damage, and enhanced the expression of muc5 mRNA on the ocular surface. We also observed anti-inflammatory effects in the tear film together with antioxidative effects in the conjunctiva, suggesting the efficacy of rebamipide in age-related dry eye disease attributable to SOD1 knockout.

AB - Purpose. To investigate the efficacy of 2% rebamipide ophthalmic solution on the tear functions and ocular surface status of the superoxide dismutase-1(Sod1-/-) mice. Methods. Two percent Rebamipide ophthalmic solution was applied to 40-week-old male Sod1-/- and wild-type (WT) mice four times a day for 2 weeks. We examined the cytokine concentrations in the tear fluid (by CytoBead assay), tear film break-up time, amount of tear production, and expressions of mucins 1, 4, and 5AC, by RT-PCR. We also performed vital staining of the ocular surface, PAS staining for muc5AC, and immunohistochemical stainings for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2′-deoxyguanosine (8-OHdG), in the conjunctiva to compare the Results before and after rebamipide instillations. Results. The tear functions and ocular surface epithelial damage scores were significantly worse in the Sod1-/- than in the WT mice. Application of 2% rebamipide for 2 weeks significantly improved the tear film break-up time, the amount of tear production, and the corneal epithelial damage scores, which also significantly increased the conjunctival goblet cell density and muc5 mRNA expression, in the Sod1-/- mice. The mean IL-6, IL-17, TNF-α, and IFN-γ levels in the tear fluid were reduced significantly along with a significant decrease in the density of cells positive for 4-HNE and 8-OHdG in the conjunctiva. Conclusions. Two percent Rebamipide ophthalmic solution significantly improved the tear stability and corneal epithelial damage, and enhanced the expression of muc5 mRNA on the ocular surface. We also observed anti-inflammatory effects in the tear film together with antioxidative effects in the conjunctiva, suggesting the efficacy of rebamipide in age-related dry eye disease attributable to SOD1 knockout.

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