title: DNA damage and repair in Fuchs endothelial corneal dystrophy.
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.
authors.affiliation: Department of Molecular Genetics, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Czarny
authors.forename: Ewelina
authors.initials: E
authors.lastname: Kasprzak
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wielgorski
authors.forename: Monika
authors.initials: M
authors.lastname: Udziela
authors.forename: Beata
authors.initials: B
authors.lastname: Markiewicz
authors.forename: Janusz
authors.initials: J
authors.lastname: Blasiak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Szaflik
authors.forename: Jacek P
authors.initials: JP
authors.lastname: Szaflik
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D003315:Cornea / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D015715:Corneal Edema / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects / Q000235:genetics; D003886:Descemet Membrane / Q000378:metabolism; D005128:Eye Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human