The Role of 2% Rebamipide Eye Drops Related to Conjunctival Differentiation in Superoxide Dismutase-1 (Sod1) Knockout Mice

Takashi Kojima, Cem Simsek, Ayako Igarashi, Kazue Aoki, Kazunari Higa, Takahiko Shimizu, Murat Dogru, Kazuo Tsubota, Jun Shimazaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Methods: Rebamipide eye drops (2%) were instilled in six 50-week-old male Sod1-/- mice and six C57BL/6 strain wild-type (WT) male mice four times a day for 2 weeks. Aqueous tear secretion quantity and tear film breakup time measurements as well as vital stainings were performed. Immunohistochemistry staining of the conjunctiva was performed using SAM pointed domain-containing ETS transcription factor (SPDEF), transglutaminase-1, and involucrin antibodies. Quantitative RT-PCR was carried out to study mRNA expression of the same markers.

Results: The mean tear quantities showed no significant changes in both mice strains after treatment (P = 0.24). The mean tear film breakup time (P = 0.003) and vital staining scores significantly improved in the Sod1-/- mice after treatment. Treatment with 2% rebamipide eye drops significantly decreased the corneal fluorescein (P = 0.0093) and Rose Bengal (P = 0.002) staining scores in the Sod1-/- mice. We showed a notable increase in SPDEF and a marked decrease in transglutaminase-1 and involucrin immunohistochemistry stainings, together with a significant increase in SPDEF (P = 0.0003) and a significant decline in transglutaminase-1 (P = 0.0072) and involucrin (P = 0.009) mRNA expression after treatment in the Sod1-/- mice.

Conclusions: Topical use of 2% rebamipide drops was observed to improve conjunctival epithelial differentiation and suppress keratinization in the Sod1-/- mice.

Purpose: The superoxide dismutase-1 knockout (Sod1-/-) mouse is an age-related dry eye mouse model. We evaluated the role of 2% rebamipide ophthalmic solution on the conjunctiva and ocular surface alterations in Sod1-/- mice.

Original languageEnglish
Pages (from-to)1675-1681
Number of pages7
JournalInvestigative ophthalmology & visual science
Volume59
Issue number3
DOIs
Publication statusPublished - 2018 Mar 1

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Ophthalmic Solutions
Knockout Mice
Tears
Staining and Labeling
Transcription Factors
Conjunctiva
Immunohistochemistry
Rose Bengal
Superoxide Dismutase-1
rebamipide
Messenger RNA
Therapeutics
Fluorescein
Inbred C57BL Mouse
Polymerase Chain Reaction
Antibodies

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

The Role of 2% Rebamipide Eye Drops Related to Conjunctival Differentiation in Superoxide Dismutase-1 (Sod1) Knockout Mice. / Kojima, Takashi; Simsek, Cem; Igarashi, Ayako; Aoki, Kazue; Higa, Kazunari; Shimizu, Takahiko; Dogru, Murat; Tsubota, Kazuo; Shimazaki, Jun.

In: Investigative ophthalmology & visual science, Vol. 59, No. 3, 01.03.2018, p. 1675-1681.

Research output: Contribution to journalArticle

Kojima, Takashi ; Simsek, Cem ; Igarashi, Ayako ; Aoki, Kazue ; Higa, Kazunari ; Shimizu, Takahiko ; Dogru, Murat ; Tsubota, Kazuo ; Shimazaki, Jun. / The Role of 2% Rebamipide Eye Drops Related to Conjunctival Differentiation in Superoxide Dismutase-1 (Sod1) Knockout Mice. In: Investigative ophthalmology & visual science. 2018 ; Vol. 59, No. 3. pp. 1675-1681.
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abstract = "Methods: Rebamipide eye drops (2{\%}) were instilled in six 50-week-old male Sod1-/- mice and six C57BL/6 strain wild-type (WT) male mice four times a day for 2 weeks. Aqueous tear secretion quantity and tear film breakup time measurements as well as vital stainings were performed. Immunohistochemistry staining of the conjunctiva was performed using SAM pointed domain-containing ETS transcription factor (SPDEF), transglutaminase-1, and involucrin antibodies. Quantitative RT-PCR was carried out to study mRNA expression of the same markers.Results: The mean tear quantities showed no significant changes in both mice strains after treatment (P = 0.24). The mean tear film breakup time (P = 0.003) and vital staining scores significantly improved in the Sod1-/- mice after treatment. Treatment with 2{\%} rebamipide eye drops significantly decreased the corneal fluorescein (P = 0.0093) and Rose Bengal (P = 0.002) staining scores in the Sod1-/- mice. We showed a notable increase in SPDEF and a marked decrease in transglutaminase-1 and involucrin immunohistochemistry stainings, together with a significant increase in SPDEF (P = 0.0003) and a significant decline in transglutaminase-1 (P = 0.0072) and involucrin (P = 0.009) mRNA expression after treatment in the Sod1-/- mice.Conclusions: Topical use of 2{\%} rebamipide drops was observed to improve conjunctival epithelial differentiation and suppress keratinization in the Sod1-/- mice.Purpose: The superoxide dismutase-1 knockout (Sod1-/-) mouse is an age-related dry eye mouse model. We evaluated the role of 2{\%} rebamipide ophthalmic solution on the conjunctiva and ocular surface alterations in Sod1-/- mice.",
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T1 - The Role of 2% Rebamipide Eye Drops Related to Conjunctival Differentiation in Superoxide Dismutase-1 (Sod1) Knockout Mice

AU - Kojima, Takashi

AU - Simsek, Cem

AU - Igarashi, Ayako

AU - Aoki, Kazue

AU - Higa, Kazunari

AU - Shimizu, Takahiko

AU - Dogru, Murat

AU - Tsubota, Kazuo

AU - Shimazaki, Jun

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Methods: Rebamipide eye drops (2%) were instilled in six 50-week-old male Sod1-/- mice and six C57BL/6 strain wild-type (WT) male mice four times a day for 2 weeks. Aqueous tear secretion quantity and tear film breakup time measurements as well as vital stainings were performed. Immunohistochemistry staining of the conjunctiva was performed using SAM pointed domain-containing ETS transcription factor (SPDEF), transglutaminase-1, and involucrin antibodies. Quantitative RT-PCR was carried out to study mRNA expression of the same markers.Results: The mean tear quantities showed no significant changes in both mice strains after treatment (P = 0.24). The mean tear film breakup time (P = 0.003) and vital staining scores significantly improved in the Sod1-/- mice after treatment. Treatment with 2% rebamipide eye drops significantly decreased the corneal fluorescein (P = 0.0093) and Rose Bengal (P = 0.002) staining scores in the Sod1-/- mice. We showed a notable increase in SPDEF and a marked decrease in transglutaminase-1 and involucrin immunohistochemistry stainings, together with a significant increase in SPDEF (P = 0.0003) and a significant decline in transglutaminase-1 (P = 0.0072) and involucrin (P = 0.009) mRNA expression after treatment in the Sod1-/- mice.Conclusions: Topical use of 2% rebamipide drops was observed to improve conjunctival epithelial differentiation and suppress keratinization in the Sod1-/- mice.Purpose: The superoxide dismutase-1 knockout (Sod1-/-) mouse is an age-related dry eye mouse model. We evaluated the role of 2% rebamipide ophthalmic solution on the conjunctiva and ocular surface alterations in Sod1-/- mice.

AB - Methods: Rebamipide eye drops (2%) were instilled in six 50-week-old male Sod1-/- mice and six C57BL/6 strain wild-type (WT) male mice four times a day for 2 weeks. Aqueous tear secretion quantity and tear film breakup time measurements as well as vital stainings were performed. Immunohistochemistry staining of the conjunctiva was performed using SAM pointed domain-containing ETS transcription factor (SPDEF), transglutaminase-1, and involucrin antibodies. Quantitative RT-PCR was carried out to study mRNA expression of the same markers.Results: The mean tear quantities showed no significant changes in both mice strains after treatment (P = 0.24). The mean tear film breakup time (P = 0.003) and vital staining scores significantly improved in the Sod1-/- mice after treatment. Treatment with 2% rebamipide eye drops significantly decreased the corneal fluorescein (P = 0.0093) and Rose Bengal (P = 0.002) staining scores in the Sod1-/- mice. We showed a notable increase in SPDEF and a marked decrease in transglutaminase-1 and involucrin immunohistochemistry stainings, together with a significant increase in SPDEF (P = 0.0003) and a significant decline in transglutaminase-1 (P = 0.0072) and involucrin (P = 0.009) mRNA expression after treatment in the Sod1-/- mice.Conclusions: Topical use of 2% rebamipide drops was observed to improve conjunctival epithelial differentiation and suppress keratinization in the Sod1-/- mice.Purpose: The superoxide dismutase-1 knockout (Sod1-/-) mouse is an age-related dry eye mouse model. We evaluated the role of 2% rebamipide ophthalmic solution on the conjunctiva and ocular surface alterations in Sod1-/- mice.

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