Evidence of oxidative stress in human corneal diseases.
This study localized malondialdehyde (MDA, a toxic byproduct of lipid peroxidation), nitrotyrosine [NT, a cytotoxic byproduct of nitric oxide (NO)], and nitric oxide synthase isomers (NOS) in normal and diseased human corneas. Normal corneas (n=11) and those with clinical and histopathological diagnoses of keratoconus (n=26), bullous keratopathy (n=17), and Fuchs' endothelial dystrophy (n=12) were examined with antibodies specific for MDA, NT, eNOS (constitutive NOS), and iNOS (inducible NOS). Normal corneas showed little or no staining for MDA, NT, or iNOS, whereas eNOS was detected in the epithelium and endothelium. MDA was present in all disease groups, with each group displaying a distinct pattern of staining. NT was detected in all keratoconus and approximately one half of Fuchs' dystrophy corneas. iNOS and eNOS were evident in all the diseased corneas. Keratoconus corneas showed evidence of oxidative damage from cytotoxic byproducts generated by lipid peroxidation and the NO pathway. Bullous keratopathy corneas displayed byproducts of lipid peroxidation but not peroxynitrite (MDA but not NT). Conversely, Fuchs' dystrophy corneas displayed byproducts of peroxynitrite with little lipid peroxidation (NT >> MDA). These data suggest that oxidative damage occurs within each group of diseased corneas. However, each disease exhibits a distinctive profile, with only keratoconus showing prominent staining for both nitrotyrosine and MDA. These results suggest that keratoconus corneas do not process reactive oxygen species in a normal manner, which may play a major role in the pathogenesis of this disease.
Buddi
Rajeev
R
The Eye Institute, Medical College of Wisconsin, Milwaukee, USA.
Lin
Brian
B
Atilano
Shari R
SR
Zorapapel
Nadia C
NC
Kenney
M Cristina
MC
Brown
Donald J
DJ
D003315:Cornea / Q000737:chemistry / Q000378:metabolism; D003316:Corneal Diseases / Q000209:etiology* / Q000378:metabolism; D004727:Endothelium / Q000737:chemistry; D004848:Epithelium / Q000737:chemistry; D005642:Fuchs' Endothelial Dystrophy / Q000378:metabolism; D006801:Humans; D007640:Keratoconus / Q000378:metabolism; D015227:Lipid Peroxidation; D008315:Malondialdehyde / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III