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MURAT DOGRU, Takashi Kojima, Taeko Nagata, Ayako Igarashi, Kazunari Higa, Yoshiyuki Satake, Seika Shimazaki, Shimizu Takahiko, Kazuo Tsubota, Jun Shimazaki; Alterations of Tear Functions and Ocular Surface Epithelial Differentiation in the SOD-1 Knock- out Mouse. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4314.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: SOD-1 knock out mouse has been reported to be a model for age related dry eye disease. We investigated the alterations in the tear function and conjunctival ocular surface epithelial differentiation in the Sod1-/- in comparison to the wild type mice.
Methods: Ten eyes of 5 Sod1-/- male mice with C57BL/background and 10 eyes of 5 C57BL6 strain wild-type male mice were examined at 10 and 50 weeks in this study. Tear film stability and corneal epithelial damage was evaluated by fluorescein and Rose Bengal stainings. Anterior segment photography was carried out at 10 to 50 weeks. Aqueous tear quantity was measured with phenol-red-impregnated cotton threads without anesthesia. Animals were sacrificed and the whole globe specimens underwent PAS and SPDEF(SAM pointed domain containing ets transcription factor) immunohistichemistry staining. Quantitative Real Time-PCR for conjunctival muc 5AC mRNA and SPDEF expression was also performed. All studies were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Statistical analysis was performed by using t test and ANOVA. A p value <1% was regarded as significance.
Results: Tear stability was significantly worse in the SOD-1 knock out mice compared to the wild type at 50 weeks. Tear stability deteriorated with aging in both mice groups. Sod1-/-mice had significantly higher vital staining scores compared to the WT at 50 weeks and the staining scores increased significantly from 10 to 50 weeks in both mice (p<0.01). Goblet cell density and SPDEF staining intensity and expression decreased significantly with aging in both mice (p<0.01).
The conjunctival ocular surface disease in the Sod1-/-mice was associated with tear instability, ocular surface epithelial damage, loss of goblet cells and decreased SPDEF expression. Alterations in the conjunctival epithelial differentation in the SOD 1 KO mice may explain the pathogenesis of the epithelial disease associated with age related dry eyes and may pave the way to alternative treatment modalities aiming epithelial differentation.
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