Advertisement
Advertise here Publish your press releases here Sponsor BioPortfolio
Follow us on Twitter Sign up for daily news and research emails Contributors wanted

Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy.

05:04 EDT 25th July 2014 | BioPortfolio

Summary of "Evidence of Oxidative Stress in the Pathogenesis of Fuchs Endothelial Corneal Dystrophy."

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.

Affiliation

From the Schepens Eye Research Institute,* Boston, Massachusetts; the Massachusetts Eye and Ear Infirmary, and the Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

Journal Details

This article was published in the following journal.

Name: The American journal of pathology
ISSN: 1525-2191
Pages:

Links

PubMed Articles [18400 Associated PubMed Articles listed on BioPortfolio]

N-Acetylcysteine Increases Corneal Endothelial Cell Survival in a Mouse Model of Fuchs Endothelial Corneal Dystrophy.

The present study evaluated survival effects of N-acetylcysteine (NAC) on cultured corneal endothelial cells exposed to oxidative and endoplasmic reticulum (ER) stress and in a mouse model of early-on...

Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy.

Fuchs endothelial dystrophy (FED) is a condition in which there is premature degeneration of corneal endothelial cells. When the number of endothelial cells is reduced to a significant degree, fluid b...

Congenital Hereditary Endothelial Dystrophy Caused by SLC4A11 Mutations Progresses to Harboyan Syndrome.

Homozygous mutations in SLC4A11 cause 2 rare recessive conditions: congenital hereditary endothelial dystrophy (CHED), affecting the cornea alone, and Harboyan syndrome consisting of corneal dystrophy...

The role of complement activation in the pathogenesis of Fuchs' dystrophy.

Inflammation can be an etiologic factor of Fuchs' dystrophy according to previous studies. Our aim was to analyse the activation of the complement system in the aqueous humor in this pathological cond...

Corneal dystrophies and genetics in the International Committee for Classification of Corneal Dystrophies era: a review.

Many of the corneal dystrophies have now been genetically characterized, and a system was established in 2008 by The International Committee for Classification of Corneal Dystrophies (IC3D) in an atte...

Clinical Trials [2653 Associated Clinical Trials listed on BioPortfolio]

Fuchs' Torsional Phaco Study

The primary objective is to compare the effect of torsional phacoemulsification and longitudinal phacoemulsification on central and peripheral corneal thickness/volume after cataract surge...

A Comparison Between Full Thickness and Partial Thickness Corneal Transplantation for Corneal Edema

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...

Study of Endothelial Keratoplasty Outcomes

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...

APEX Study: Effects of Allopurinol on Coronary and Peripheral Endothelial Function in Patients With Cardiac Syndrome X

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...

The Role of Oxidative Stress in the Cardiovascular Consequences of Sleep Apnea

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...

Medical and Biotech [MESH] Definitions

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.

Search BioPortfolio: