RGD Reference Report - The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice. - Rat Genome Database

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

Authors: Ohguchi, T  Kojima, T  Ibrahim, OM  Nagata, T  Shimizu, T  Shirasawa, T  Kawakita, T  Satake, Y  Tsubota, K  Shimazaki, J  Ishida, S 
Citation: Ohguchi T, etal., Invest Ophthalmol Vis Sci. 2013 Nov 21;54(12):7793-802. doi: 10.1167/iovs.13-13128.
RGD ID: 8655609
Pubmed: PMID:24168989   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.13-13128   (Journal Full-text)

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-alpha, and IFN-gamma 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dry eye syndrome  ISOSod1 (Mus musculus)8655609; 8655609 RGD 
dry eye syndrome  IMP 8655609 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Genes (Mus musculus)
Sod1  (superoxide dismutase 1, soluble)

Genes (Homo sapiens)
SOD1  (superoxide dismutase 1)


Additional Information