title: Cell response to oxidative stress induced apoptosis in patients with Leber's hereditary optic neuropathy.
abstract: OBJECTIVE
  Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease in which acute or subacute bilateral visual loss occurs preferentially in young men. Over 95% of LHON cases are associated with one of three mitochondrial DNA (mtDNA) point mutations, but only 50% of men and 10% of women who harbour a pathogenetic mtDNA mutation develop optic neuropathy. This incomplete penetrance and preference for men suggests that additional genetic (nuclear or mitochondrial) and/or environmental factors must modulate phenotype expression in LHON. A role for reactive oxygen species (ROS) in mitochondrial diseases, secondary to mtDNA mutations, or as a result of the direct effect of ROS cytotoxicity, has been implicated in many mitochondrial disorders, including LHON. The purpose of this study was to investigate the role of oxidative stress induced apoptosis in LHON.
  
  
  METHODS
  The 2-deoxy-D-ribose induced apoptotic response of peripheral blood lymphocytes from six patients with LHON and six healthy subjects was investigated using light microscopy, flow cytometry, agarose gel electrophoresis, and the measurement of mitochondrial membrane potential.
  
  
  RESULTS
  Cells of patients with LHON had a higher rate of apoptosis than those of controls and there was evidence of mitochondrial involvement in the activation of the apoptotic cascade.
  
  
  CONCLUSIONS
  These differences in oxidative stress induced apoptosis are in line with the hypothesis that redox homeostasis could play a role in the expression of genetic mutations in different individuals and could represent a potential target in the development of new therapeutic strategies.
authors.affiliation: Department of Neurological and Behavioural Sciences, University of Siena, Siena, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Battisti
authors.forename: P
authors.initials: P
authors.lastname: Formichi
authors.forename: E
authors.initials: E
authors.lastname: Cardaioli
authors.forename: S
authors.initials: S
authors.lastname: Bianchi
authors.forename: P
authors.initials: P
authors.lastname: Mangiavacchi
authors.forename: S A
authors.initials: SA
authors.lastname: Tripodi
authors.forename: P
authors.initials: P
authors.lastname: Tosi
authors.forename: A
authors.initials: A
authors.lastname: Federico
mesh_terms: D000963:Antimetabolites / Q000494:pharmacology; D017209:Apoptosis; D016022:Case-Control Studies; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D003847:Deoxyglucose / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D008214:Lymphocytes; D029242:Optic Atrophy, Hereditary, Leber / Q000503:physiopathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
chemical_list: D000963:Antimetabolites; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D003847:Deoxyglucose