TY - JOUR
T1 - Mitochondrial abnormalities in patients with LHON-like optic neuropathies
AU - Abu-Amero, Khaled K.
AU - Bosley, Thomas M.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/10
Y1 - 2006/10
N2 - PURPOSE. To investigate certain biochemical and molecular characteristics of mitochondria in patients with Leber hereditary optic neuropathy (LHON)-like optic neuropathies. METHODS. Patients who had LHON-like optic neuropathies in both eyes were selected from neuro-ophthalmology clinics. Evaluation included clinical examination, neuroimaging, and assessment of several mitochondrial parameters in the blood, including sequencing the entire mitochondrial (mt)DNA coding region, measuring relative mtDNA content, studying mitochondrial respiratory function in some patients, and sequencing the OPA1 and OPA3 genes. RESULTS. Thirty-five patients (21 men and 14 women; average age at onset 19.0 ± 8.7 years) met inclusion and exclusion criteria for LHON-like optic neuropathies with median visual acuity approximately 20/200. Other hereditary retinopathies and optic neuropathies were unlikely because of inclusion and exclusion criteria, because ERGs were normal, and because no patient had pathogenic sequence changes in the OPA1 or OPA3 genes. Compared with control subjects, these patients had more potentially pathogenic nonsynonymous mtDNA changes, greater relative mtDNA content (P < 0.001), and less mitochondrial respiratory activity (P < 0.001). Only six patients (17%) had primary LHON mutations; however, even the 29 patients without primary LHON mutations had significant evidence of mitochondrial abnormalities. Mitochondrial haplo-group distribution was similar in patients and control subjects. CONCLUSIONS. Primary LHON mutations are less common in patients with LHON-like optic neuropathy selected from a clinical setting than in patients with LHON from multigenerational families. The results suggest that mitochondrial dysfunction plays a role in this type of optic neuropathy whether or not primary LHON mutations are present. This information has implications for diagnostic testing and for future investigations into mechanisms of disease.
AB - PURPOSE. To investigate certain biochemical and molecular characteristics of mitochondria in patients with Leber hereditary optic neuropathy (LHON)-like optic neuropathies. METHODS. Patients who had LHON-like optic neuropathies in both eyes were selected from neuro-ophthalmology clinics. Evaluation included clinical examination, neuroimaging, and assessment of several mitochondrial parameters in the blood, including sequencing the entire mitochondrial (mt)DNA coding region, measuring relative mtDNA content, studying mitochondrial respiratory function in some patients, and sequencing the OPA1 and OPA3 genes. RESULTS. Thirty-five patients (21 men and 14 women; average age at onset 19.0 ± 8.7 years) met inclusion and exclusion criteria for LHON-like optic neuropathies with median visual acuity approximately 20/200. Other hereditary retinopathies and optic neuropathies were unlikely because of inclusion and exclusion criteria, because ERGs were normal, and because no patient had pathogenic sequence changes in the OPA1 or OPA3 genes. Compared with control subjects, these patients had more potentially pathogenic nonsynonymous mtDNA changes, greater relative mtDNA content (P < 0.001), and less mitochondrial respiratory activity (P < 0.001). Only six patients (17%) had primary LHON mutations; however, even the 29 patients without primary LHON mutations had significant evidence of mitochondrial abnormalities. Mitochondrial haplo-group distribution was similar in patients and control subjects. CONCLUSIONS. Primary LHON mutations are less common in patients with LHON-like optic neuropathy selected from a clinical setting than in patients with LHON from multigenerational families. The results suggest that mitochondrial dysfunction plays a role in this type of optic neuropathy whether or not primary LHON mutations are present. This information has implications for diagnostic testing and for future investigations into mechanisms of disease.
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U2 - 10.1167/iovs.06-0295
DO - 10.1167/iovs.06-0295
M3 - Article
C2 - 17003408
AN - SCOPUS:33750593212
VL - 47
SP - 4211
EP - 4220
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 10
ER -