Oxidative Stress Profile in Genetically Confirmed Cases of Leber's Hereditary Optic Neuropathy

J Mol Neurosci. 2021 May;71(5):1070-1081. doi: 10.1007/s12031-020-01729-y. Epub 2020 Oct 23.


The mechanisms of the complex pathophysiology of Leber's hereditary optic neuropathy (LHON) are still insufficiently clarified. The role of oxidative stress as an etiological factor has been proposed and demonstrated in vitro, but without conclusive data that rely on clinical samples. The aim of the study was to evaluate and characterize the existence of oxidative stress in the plasma of LHON patients and healthy individuals. Whole mitochondrial genome sequencing has been performed in order to identify primary LHON mutations. For the assessment of oxidative stress, the following biomarkers were determined in plasma: total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), while oxidative damage of cellular proteins was estimated by quantifying advanced oxidation protein products (AOPP). All three primary LHON mutations (m.3460G > A, m.11778G > A and m.14484 T > C) were identified as a genetic cause of the disease, where the most prevalent one was m.11778G > A. LHON patients have a highly significant increase of TOS and a marked decrease of TAS levels, which suggests the existence of substantial oxidative stress. OSI is high in LHON patients, which definitely implies the presence of redox imbalance. Elevated level of AOPP in LHON patients refers to the significant deleterious effects of oxidative stress on cellular proteins. Oxidative stress parameters do not significantly differ between LHON individuals with different primary mutations. Both symptomatic and asymptomatic LHON patients have an augmented level of oxidative stress which suggests that primary mutations exhibit a pro-oxidative phenotype. Gender and smoking habit significantly influence examined biochemical parameters when LHON patients are compared with the control group. Different mitochondrial haplogroups are characterized by altered levels of OSI in LHON group. The absence of physiological correlations between redox parameters reflects the deregulation of homeostatic oxidative/antioxidative balance in LHON patients. This is the greatest series of LHON patients that were evaluated for oxidative stress and the first case-controlled study that evaluated TOS, TAS, OSI, and AOPP and their influence on disease phenotype. It is evident that the presence of oxidative stress represents an important pathophysiological event in LHON and that it could potentially serve as a circulatory biomarker for a therapy efficacy understanding.

Keywords: Leber’s hereditary optic neuropathy; Mitochondria; Mutation; Oxidative stress.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • DNA, Mitochondrial / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Optic Atrophy, Hereditary, Leber / genetics
  • Optic Atrophy, Hereditary, Leber / metabolism*
  • Optic Atrophy, Hereditary, Leber / pathology
  • Oxidative Stress*
  • Pedigree


  • DNA, Mitochondrial