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PLoS One. 2014 Jul 18;9(7):e99328. doi: 10.1371/journal.pone.0099328. eCollection 2014.

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

Author information

1
Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.
2
Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan; Tokyo Dental College, Department of Ophthalmology, Chiba, Japan.
3
Tokyo Dental College, Department of Ophthalmology, Chiba, Japan.
4
Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine; Chiba, Japan.

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.

PMID:
25036096
PMCID:
PMC4103776
DOI:
10.1371/journal.pone.0099328
[Indexed for MEDLINE]
Free PMC Article

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