Leber Hereditary Optic Neuropathy: A Mitochondrial Disease Unique in Many Ways

Handb Exp Pharmacol. 2017;240:309-336. doi: 10.1007/164_2016_1.


Leber hereditary optic neuropathy (LHON) was the first mitochondrial disease to be identified as being caused by mutations in the mitochondrial DNA (mtDNA). This disease has been studied extensively in the past two decades, particularly in Brazilian, Chinese and European populations; and many primary mutations have been reported. However, the disease is enigmatic with many unique features, and there still are several important questions to be resolved. The incomplete penetrance, the male-biased disease expression and the prevalence in young adults all defy a proper explanation. It has been reported that the development of LHON is affected by the interaction between mtDNA mutations, mtDNA haplogroup background, nuclear genes, environmental factors and epigenetics. Furthermore, with the help of new animal models for LHON that have been created in recent years, we are continuing to learn more about the mechanism of this disease. The stage has now been reached at which there is a good understanding of both the genetic basis of the disease and its epidemiology, but just how the blindness that follows from the death of cells in the optic nerve can be prevented remains to be a pharmacological challenge. In this chapter, we summarize the progress that has been made in various recent studies on LHON, focusing on the molecular pathogenic mechanisms, clinical features, biochemical effects, the pharmacology and its treatment.

Keywords: Animal model; LHON; Nuclear genes; Therapy; mtDNA.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA, Mitochondrial / genetics*
  • Gene Editing
  • Genetic Therapy
  • Humans
  • Mutation*
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Optic Atrophy, Hereditary, Leber / therapy


  • DNA, Mitochondrial