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Takashi Kojima, Cem Simsek, Ayako Igarashi, Kazue Aoki, Kazunari Higa, Takahiko Shimizu, Murat Dogru, Kazuo Tsubota, Jun Shimazaki; The Role of 2% Rebamipide Eye Drops Related to Conjunctival Differentiation in Superoxide Dismutase-1 (Sod1) Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2018;59(3):1675-1681. doi: https://doi.org/10.1167/iovs.17-23213.
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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.
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.
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.
Topical use of 2% rebamipide drops was observed to improve conjunctival epithelial differentiation and suppress keratinization in the Sod1−/− mice.
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