摘要
Objectives: Leber’s hereditary optic neuropathy (LHON)is a maternally inher ited disease in which acute or subacute bilateral visual loss occurs preferentia lly in young men. Over 95%of LHON cases are associated with one of three mitoch ondrial DNA (mtDNA) point mutations, but only 50%of men and 10%of women who ha rbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete pe netrance and preference for men suggests that additional genetic (nuclear or mit ochondrial) and/or environmental factors must modulate phenotype expression in L HON. A role for reactive oxygen species (ROS) in mitochondrial diseases, seconda ry to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpo se of this study was toinvestigate the role of oxidative stressinduced apoptosis in LHON. Methods: The 2-deoxyDribose induced apoptotic response of periphe ral blood lymphocytes from six patients with LHON and six healthy subjects was i nvestigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential. Results: Cells of pati ents with LHON had a higher rate of apoptosis than those of controls and there w as evidence of mitochondrial involvement in the activation of the apoptotic casc ade. Conclusions: These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expres sion of genetic mutations in different individuals and could represent a potenti al target in the development of new therapeutic strategies.
Objectives: Leber’s hereditary optic neuropathy (LHON)is a maternally inher ited disease in which acute or subacute bilateral visual loss occurs preferentia lly in young men. Over 95%of LHON cases are associated with one of three mitoch ondrial DNA (mtDNA) point mutations, but only 50%of men and 10%of women who ha rbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete pe netrance and preference for men suggests that additional genetic (nuclear or mit ochondrial) and/or environmental factors must modulate phenotype expression in L HON. A role for reactive oxygen species (ROS) in mitochondrial diseases, seconda ry to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpo se of this study was toinvestigate the role of oxidative stressinduced apoptosis in LHON. Methods: The 2-deoxyDribose induced apoptotic response of periphe ral blood lymphocytes from six patients with LHON and six healthy subjects was i nvestigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential. Results: Cells of pati ents with LHON had a higher rate of apoptosis than those of controls and there w as evidence of mitochondrial involvement in the activation of the apoptotic casc ade. Conclusions: These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expres sion of genetic mutations in different individuals and could represent a potenti al target in the development of new therapeutic strategies.
