DNA damage and repair in Fuchs endothelial corneal dystrophy

Piotr Czarny,Janusz Blasiak,Beata Markiewicz,Jacek P. Szaflik,Ewelina Kasprzak,Mariusz Wielgorski,Jerzy Szaflik,Monika Udziela

doi:10.1007/s11033-012-2369-2

Abstract

Fuchs endothelial corneal dystrophy (FECD) is a slowly progressive eye disease leading to blindness, mostly affecting people above 40 years old. The only known method of curing FECD is corneal transplantation. The disease is characterized by the presence of extracellular deposits called “cornea guttata”, apoptosis of corneal endothelial cells, dysfunction of Descement’s membrane and corneal edema. Oxidative stress is suggested to play a role in FECD pathogenesis. Reactive oxygen species produced during the stress may damage biomolecules, including DNA. In the present study we evaluated the extent of endogenous DNA damage, including oxidatively modified DNA bases, and damage induced by hydrogen peroxide as well as the kinetics of DNA repair in peripheral blood mononuclear cells of 50 patients with FECD and 43 age-matched controls without visual disturbances. To quantify DNA damage and repair we used the alkaline comet assay technique with the enzymes recognizing oxidative DNA damage, hOGG1 and EndoIII. We did not observe differences in the extent of endogenous and hydrogen peroxide-induced DNA damage between FECD patients and controls. However, we found a lower efficacy of DNA repair in FECD patients as compared with control individuals. The results obtained suggest that the lowering of the DNA repair capacity may be one of the mechanisms underlying the role of oxidative stress in the FECD pathology.

Highlights

Fuchs endothelial corneal dystrophy (FECD, Online Mendelian Inheritance in Man [1] no. 136800) is a bilateral, often asymmetric, slowly progressive blinding disease, which was first described by Fuchs in 1910 [2]
In the present study we evaluated the extent of endogenous DNA damage, including oxidatively modified DNA bases, and damage induced by hydrogen peroxide as well as the kinetics of DNA repair in peripheral blood mononuclear cells of 50 patients with FECD and 43 agematched controls without visual disturbances
The aim of our work was to evaluate the extent of endogenous DNA damage, the susceptibility to oxidative DNA damage induced by hydrogen peroxide and efficiency of DNA damage repair in patients with FECD as compared to the control group without vision impairment

Summary

Introduction

Fuchs endothelial corneal dystrophy (FECD, Online Mendelian Inheritance in Man [1] no. 136800) is a bilateral, often asymmetric, slowly progressive blinding disease, which was first described by Fuchs in 1910 [2]. It is estimated that FECD affects more than 4 % of the population above 40 years old and is the most common indication for corneal transplantation, the only known method of curing this disease, in many countries, including the US [3,4,5]. It more often affects women than men [3]. FECD can be classified as a ‘‘classic’’ (late-onset) or as a familiar (early-onset). Data suggesting that the COL8A2 mutation is responsible for late-onset FECD are not conclusive [7, 8]

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