This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (12)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Ophthalmology, Other  • Articles for Residents  • Alert me on articles by topic

Qian J. Li, MD; M. Farooq Ashraf, MD; DeFen Shen, PhD; W. Richard Green, MD; Walter J. Stark, MD; Chi-Chao Chan, MD; Terrence P. O'Brien, MD

Arch Ophthalmol. 2001;119:1597-1604.

Objective  To investigate the potential role of apoptosis in the pathogenesis of Fuchs endothelial dystrophy of the cornea.

Methods  Twenty-one corneal buttons from patients with Fuchs dystrophy and 15 control corneas were studied. Apoptosis was assessed by the in situ end-labeling of double-stranded DNA breaks, and by immunohistochemical characterization of cellular markers associated with apoptosis (Fas, FasL, Bcl-2, and Bax). Expression of Bcl-2 and Bax mRNA in the corneal stroma and endothelium was separately analyzed by a semiquantitative reverse transcriptase polymerase chain reaction. Furthermore, cultivated keratocytes generated from diseased corneal buttons and donor rims were exposed to camptothecin, an apoptotic inducer, for 6 and 24 hours. They were then examined for protein and messenger RNA (mRNA) expression of apoptotic regulatory molecules.

Results  DNA fragmentation was seen in the epithelium, stroma, and endothelium in 6 of 7 corneas with Fuchs dystrophy. A statistically significant difference was identified in the expression of Bax and its mRNA in the stroma, but not in the endothelium of Fuchs dystrophy corneas. Following exposure to camptothecin, keratocytes from patients with Fuchs dystrophy responded with an increased level of Bax and a low level of Bcl-2. This trend was distinctively different from the response of normal keratocytes.

Conclusions  The evidence in this study points to a disease-related disturbance in the regulation of apoptosis in Fuchs dystrophy. Our findings suggest that excessive apoptosis may be an important mechanism in the pathogenesis of Fuchs dystrophy.

From Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, Md (Drs Li, Ashraf, Green, Stark, and O'Brien); and the Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Md (Drs Shen and Chan). The authors have no proprietary interest in any of the procedures or products mentioned in this article.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Increased Clusterin Expression in Fuchs' Endothelial Dystrophy
Jurkunas et al.
IOVS 2008;49:2946-2955.
ABSTRACT | FULL TEXT  

Decreased Expression of Peroxiredoxins in Fuchs' Endothelial Dystrophy
Jurkunas et al.
IOVS 2008;49:2956-2963.
ABSTRACT | FULL TEXT  

Hypoxia Protects Human Corneal Endothelium from Tertiary Butyl Hydroperoxide and Paraquat-Induced Cell Death In Vitro
Cheng et al.
Exp. Biol. Med. 2007;232:445-453.
ABSTRACT | FULL TEXT  

Developmentally Regulated Expression of Sp1 in the Mouse Cornea
Nakamura et al.
IOVS 2005;46:4092-4096.
ABSTRACT | FULL TEXT  

Targeted disruption of Col8a1 and Col8a2 genes in mice leads to anterior segment abnormalities in the eye
Hopfer et al.
FASEB J. 2005;19:1232-1244.
ABSTRACT | FULL TEXT  

Inheritance of a Novel COL8A2 Mutation Defines a Distinct Early-Onset Subtype of Fuchs Corneal Dystrophy
Gottsch et al.
IOVS 2005;46:1934-1939.
ABSTRACT | FULL TEXT  

Predicting Endothelial Cell Loss and Long-Term Corneal Graft Survival
Armitage et al.
IOVS 2003;44:3326-3331.
ABSTRACT | FULL TEXT  

Mechanisms of staurosporine induced apoptosis in a human corneal endothelial cell line
Thuret et al.
Br. J. Ophthalmol. 2003;87:346-352.
ABSTRACT | FULL TEXT