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Osama Ibrahim, Murat Dogru, Takashi Kojima, Yukihiro Matsumoto, Tais Wakamatsu, Ayako Igarashi, Takahiko Shimizu, Jun Shimazaki, Kazuo Tsubota; Evidence For Accelerated Apoptosis And Altered Meibomian Glandular Differentiation In The Sod1 Knock-out Mice Novel Model For Age Related Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3771.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of our study was to investigate the alterations of the meibomian gland (MG) in (SOD1)-deficient (-/-) mice.
Tear function tests [Break up time (BUT) and cotton thread] and corneal fluorescein staining tests were performed on SOD1-deficient (-/-) male mice (n=24) aged 10 and 50 weeks and age and sex matched wild-type (+/+) mice (n=25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O staining, TUNEL staining, immunohistochemistry stainings for 4-HNE, 8-OHdG, CD45 and Ki67. Transmission electron microscopic examination (TEM) was also performed. The study was conducted in compliance with ARVO statement for the use of animals in Ophthalmic and Visual Research.
The mean BUT and tear quantity values in SOD1-deficient (-/-) mice were significantly lower compared with wild-type mice throughout the follow up. Fluorescein staining scores were significantly higher in the SOD1-deficient (-/-) mice compared to the wild-type mice. Tear and serum IL-6 and TNF-alpha also showed significant time wise elevations in the SOD1-deficient (-/-) mice. Oil Red O staining showed an accumulation of large lipid droplets in the SOD1-deficient (-/-) mice from 10 to 50 weeks. Immunohistochemistry revealed increased TUNEL, oxidative stress marker stainings of the MG acinar epithelium and decreased staining for Ki67 in the SOD1-deficient (-/-) mice compared to the wild-type mice. Immunohistochemistry staining for CD45 showed an increased staining from 10 to 50 weeks in the SOD1-deficient (-/-) mice compared to the wild-type mice. TEM revealed prominent mitochondrial changes in the SOD1-deficient (-/-) mice.
The SOD1-deficient (-/-) mouse appears to be a promising model for the study of age related meibomian gland alterations.
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