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 journalArticlepeer-review

8 Citations (Scopus)


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. 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.

Original languageEnglish
Pages (from-to)1675-1681
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Issue number3
Publication statusPublished - 2018 Mar


  • Conjunctiva
  • Dry eye
  • Keratinization
  • Rebamipide
  • Secretagogue

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'The role of 2% rebamipide eye drops related to conjunctival differentiation in superoxide dismutase-1 (Sod1) knockout mice'. Together they form a unique fingerprint.

Cite this