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

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.

• Authors: Osama M A Ibrahim, Murat Dogru, Yukihiro Matsumoto, Ayako Igarashi, Takashi Kojima, Tais Hitomi Wakamatsu, Takaaki Inaba, Takahiko Shimizu, Jun Shimazaki, Kazuo Tsubota
• Journal: PloS one (PLoS One) Vol. 9 Issue 7 Pg. e99328 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25036096 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Age Factors
• Animals
• Apoptosis
• DNA Damage
• Dry Eye Syndromes (etiology, physiopathology)
• Epithelium, Corneal (pathology)
• Inflammation
• Interleukin-6 (blood)
• Lipid Peroxidation
• Male
• Meibomian Glands (enzymology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Oxidative Stress
• Superoxide Dismutase (deficiency)
• Superoxide Dismutase-1
• Tears (chemistry, metabolism)
• Tumor Necrosis Factor-alpha (blood)