Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice

Osama M.A. Ibrahim, Murat Dogru, Yukihiro Matsumoto, Ayako Igarashi, Takashi Kojima, Tais Hitomi Wakamatsu, Takaaki Inaba, Takahiko Shimizu, Jun Shimazaki, Kazuo Tsubota

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Abstract

Purpose: The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1 -/-) mouse. Methods: Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1 -/- 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 lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. Results: Corneal vital staining scores in the Sod1-/- mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1-/- mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1-/- mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1-/- mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1-/- mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1-/- mice. Conclusions: Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1-/- mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.

Original languageEnglish
Article numbere99328
JournalPloS one
Volume9
Issue number7
DOIs
Publication statusPublished - 2014 Jul 18

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Ibrahim, O. M. A., Dogru, M., Matsumoto, Y., Igarashi, A., Kojima, T., Wakamatsu, T. H., Inaba, T., Shimizu, T., Shimazaki, J., & Tsubota, K. (2014). Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice. PloS one, 9(7), [e99328]. https://doi.org/10.1371/journal.pone.0099328