Oxidative deoxyribonucleic acid damage in the eyes of glaucoma patients.
BACKGROUND
Little is known about the molecular mechanisms responsible for the development of glaucoma, the leading cause of irreversible blindness worldwide. Some investigators have hypothesized that oxidative damage may be involved. We evaluated oxidative deoxyribonucleic acid (DNA) damage, in terms of 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the eyes of glaucoma patients.


METHODS
Levels of 8-OH-dG were measured in the trabecular meshwork region from 42 patients with glaucoma and 45 controls of similar age and sex. Genotypes of glutathione S-transferase isoenzymes (GSTM1 and GSTT1) were assessed by polymerase chain reaction in the same DNA samples.


RESULTS
Levels of 8-OH-dG were significantly higher in glaucoma patients than in controls. Oxidative DNA damage in patients with glaucoma correlated significantly with intraocular pressure; in patients with primary open-angle glaucoma, it also correlated with visual field defects. GSTT1 was similar in the two groups, and had no effect on 8-OH-dG levels. Conversely, 8-OH-dG levels were significantly higher in GSTM1-null than in GSTM1-positive subjects. The GSTM1-null genotype was significantly more common in patients with primary open-angle glaucoma than in controls.


CONCLUSIONS
Oxidative DNA damage is significantly increased in the trabecular meshwork of glaucoma patients. GSTM1 gene deletion, which has been associated with an increased risk of cancer at various sites and molecular lesions in atherosclerosis, predisposes to more severe oxidative DNA damage in glaucoma patients. These findings may contribute to understanding the pathogenesis of glaucoma and may be useful in the prevention and treatment of this disease.
Izzotti
Alberto
A
Department of Health Sciences, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy
Saccà
Sergio C
SC
Cartiglia
Cristina
C
De Flora
Silvio
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D017353:Gene Deletion; D005901:Glaucoma / Q000235:genetics / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D014129:Trabecular Meshwork / Q000378:metabolism*
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1