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May-Yung Yen, Shu-Huei Kao, An-Guor Wang, Yau-Huei Wei; Increased 8-Hydroxy-2′-Deoxyguanosine in Leukocyte DNA in Leber’s Hereditary Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2004;45(6):1688-1691. doi: 10.1167/iovs.03-0568.
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purpose. This study was conducted to test the hypothesis that oxidative stress is involved in the pathogenesis of Leber’s hereditary optic neuropathy (LHON). The level of 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidized DNA base common in cells undergoing oxidative stress, was measured in leukocyte DNA from patients with LHON and normal control subjects.
methods. The 8-OHdG and deoxyguanosine (dG) content in leukocyte DNA from 25 patients with LHON with an 11778 mitochondrial (mt)DNA mutation, 14 asymptomatic maternal relatives, and 27 unrelated normal control subjects were measured using high-performance liquid chromatography and electrochemical detection methods.
results. The mean 8-OHdG/105 dG ratio from leukocyte DNA was 1.34 ± 0.99 in patients with LHON, 1.00 ± 0.91 in their asymptomatic maternal relatives, and 0.31 ± 0.20 in normal control subjects, respectively. There was a statistically significant difference in the mean 8-OHdG/105 dG ratio between patients with LHON and normal control subjects and between asymptomatic maternal relatives and normal control subjects. The difference between patients with LHON and asymptomatic maternal relatives did not reach statistical significance.
conclusions. Patients with LHON with an 11778 mtDNA mutation had higher oxidative DNA damage. Oxidative stress has a key role in the pathogenesis of LHON.
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