Track topics on Twitter Track topics that are important to you
Fuchs endothelial corneal dystrophy (FECD) is a progressive, blinding disease characterized by corneal endothelial (CE) cell apoptosis. Corneal transplantation is the only measure currently available to restore vision in these patients. Despite the identification of some genetic factors, the pathophysiology of FECD remains unclear. In this study, we observed a decrease in the antioxidant response element-driven antioxidants in FECD corneal endothelium. We further demonstrated that nuclear factor erythroid 2-related factor 2, a transcription factor known to bind the antioxidant response element and activate antioxidant defense, is down-regulated in FECD endothelium. Importantly, we detected significantly higher levels of oxidative DNA damage and apoptosis in FECD endothelium compared with normal controls and pseudophakic bullous keratopathy (iatrogenic CE cell loss) specimens. A marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, colocalized to mitochondria, indicating that the mitochondrial genome is the specific target of oxidative stress in FECD. Oxidative DNA damage was not detected in pseudophakic bullous keratopathy corneas, whereas it colocalized with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells in FECD samples. Ex vivo, oxidative stress caused characteristic morphological changes and apoptosis of CE, suggestive of findings that characterize FECD in vivo. Together, these data suggest that suboptimal nuclear factor erythroid 2-related factor 2-regulated defenses may account for oxidant-antioxidant imbalance in FECD, which in turn leads to oxidative DNA damage and apoptosis. This study provides evidence that oxidative stress plays a key role in FECD pathogenesis.
From the Schepens Eye Research Institute,* Boston, Massachusetts; the Massachusetts Eye and Ear Infirmary, and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
This article was published in the following journal.
Name: The American journal of pathology
To investigate the effect of mutations in SLC4A11 on cellular localization of the protein, mitochondrial function, and apoptosis due to oxidative stress. Mutations in SLC4A11 have been associated with...
Fuchs' endothelial corneal dystrophy (FECD), which affects approximately 5% of the population over 40 in the U.S.A., is a major cause of corneal transplantation. FECD is associated with mutations of a...
In various corneal injuries (such as chemical burns or irradiation of corneas with UVB radiation) and ocular diseases (e.g. dry eye disease, keratokonus, bullous keratopathy, Fuchs´endothelial dystro...
A meta-analysis of TCF4 and PTPRG gene variants in Fuchs' corneal dystrophy (FCD).
The aim of this study was to describe the clinical course in Fuchs dystrophy where the central Descemet membrane was removed and not replaced with donor tissue.
The primary objective is to compare the effect of torsional phacoemulsification and longitudinal phacoemulsification on central and peripheral corneal thickness/volume after cataract surge...
The objectives of this study are to compare the visual and refractive outcomes of deep lamellar endothelial keratoplasty (DLEK) with penetrating keratoplasty as treatment for certain cases...
Endothelial keratoplasty is a cornea-sparing transplant technique that replaces only the diseased endothelial cell layer of the patient's cornea. This technique offers many advantages com...
Morbidity of patients with cardiac syndrome X (typical anginal-like chest pain and normal coronary arteriograms) is high with continuing episodes of chest pain and frequent hospital readmi...
Obstructive Sleep Apnea (OSA) is the most common sleep disorder affecting up to 9-24 % of middle aged adults, and is becoming increasingly implicated in the pathogenesis of hypertension, a...
Loss of CORNEAL ENDOTHELIUM usually following intraocular surgery (e.g., cataract surgery) or due to FUCHS' ENDOTHELIAL DYSTROPHY; ANGLE-CLOSURE GLAUCOMA; IRITIS; or aging.
Disorder caused by loss of endothelium of the central cornea. It is characterized by hyaline endothelial outgrowths on Descemet's membrane, epithelial blisters, reduced vision, and pain.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
An autosomal dominant form of hereditary corneal dystrophy due to a defect in cornea-specific KERATIN formation. Mutations in the genes that encode KERATIN-3 and KERATIN-12 have been linked to this disorder.
A direct-acting oxidative stress-inducing agent used to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. It is also used as a catalyst in polymerization reactions and to introduce peroxy groups into organic molecules.
Latest News Clinical Trials Research Drugs Reports Corporate
Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...