Oxidative Stress Induced Age Dependent Meibomian Gland Dysfunction in Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice

被引:75
作者
Ibrahim, Osama M. A. [1 ]
Dogru, Murat [1 ,2 ]
Matsumoto, Yukihiro [1 ]
Igarashi, Ayako [2 ]
Kojima, Takashi [1 ]
Wakamatsu, Tais Hitomi [1 ]
Inaba, Takaaki [1 ]
Shimizu, Takahiko [2 ,3 ]
Shimazaki, Jun
Tsubota, Kazuo [1 ]
机构
[1] Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan
[2] Tokyo Dent Coll, Dept Ophthalmol, Chiba, Japan
[3] Chiba Univ, Grad Sch Med, Dept Adv Aging Med, Chiba, Japan
来源
PLOS ONE | 2014年 / 9卷 / 07期
基金
日本学术振兴会;
关键词
NECROSIS-FACTOR-ALPHA; DRY EYE DISEASE; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; SJOGRENS-SYNDROME; LACRIMAL GLAND; MUSCLE ATROPHY; CYTOCHROME-C; MITOCHONDRIAL; DAMAGE;
D O I
10.1371/journal.pone.0099328
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-alpha 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.
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页数:13
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