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  • Title: Mitochondrial changes in leukocytes of patients with optic neuritis.
    Author: Bosley TM, Constantinescu CS, Tench CR, Abu-Amero KK.
    Journal: Mol Vis; 2007 Aug 29; 13():1516-28. PubMed ID: 17893651.
    Abstract:
    PURPOSE: Optic neuritis (ON) is a demyelinating disorder affecting optic nerves. It has certain similarities to Leber hereditary optic neuropathy (LHON) and other spontaneous optic neuropathies known to be associated with mitochondriopathies. We evaluated patients with optic neuritis for evidence of systemic mitochondrial abnormalities. METHODS: Patients were selected who had ON affecting one or both eyes. We performed clinical examinations and neuroimaging on the participants. We sequenced the entire mitochondrial DNA (mtDNA) genome except for the D-loop in leukocytes of all patients; assessed relative mtDNA content; measured mitochondrial respiratory function in 15 patients; and sequenced OPA1 and OPA3 genes, where mutations have been associated with dominant and recessive optic nerve atrophy, respectively. RESULTS: Twenty-six patients (11 males and 15 females; average age at onset 23.4+/-8.1 years) met inclusion and exclusion criteria. Eleven patients had neuroimaging evidence of disseminated demyelination, and six had clinically definite multiple sclerosis. No patient had a primary LHON mutation or a pathologic sequence change in OPA1 or OPA3 genes. Sixteen patients had potentially pathologic mtDNA changes, and after recovery these patients had significantly worse visual acuity (p=0.002) and color vision (p = 0.009) than other patients. Mean relative mtDNA content was significantly increased in ON patients compared to controls (2.39 versus 1.03; p<0.001), while mitochondrial respiratory activity was significantly decreased (16.78 versus 22.53; p<0.001). CONCLUSIONS: The presence of these systemic mitochondrial abnormalities in patients with ON suggests that mitochondrial abnormalities may constitute risk factors for the occurrence and severity of ON.
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