Emerging model systems and treatment approaches for Leber's hereditary optic neuropathy: Challenges and opportunities

Biochim Biophys Acta Mol Basis Dis. 2020 Jun 1;1866(6):165743. doi: 10.1016/j.bbadis.2020.165743. Epub 2020 Feb 24.


Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease mainly affecting retinal ganglion cells (RGCs). The pathogenesis of LHON remains ill-characterized due to a historic lack of effective disease models. Promising models have recently begun to emerge; however, less effective models remain popular. Many such models represent LHON using non-neuronal cells or assume that mutant mtDNA alone is sufficient to model the disease. This is problematic because context-specific factors play a significant role in LHON pathogenesis, as the mtDNA mutation itself is necessary but not sufficient to cause LHON. Effective models of LHON should be capable of demonstrating processes that distinguish healthy carrier cells from diseased cells. In light of these considerations, we review the pathophysiology of LHON as it relates to old, new and future models. We further discuss treatments for LHON and unanswered questions that might be explored using these new model systems.

Keywords: Induced pluripotent stem cells; Leber's hereditary optic neuropathy; Mitochondrial disease; Retinal ganglion cells.

Publication types

  • Review

MeSH terms

  • Cells, Cultured
  • DNA, Mitochondrial / genetics*
  • Humans
  • Mitochondria / genetics*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Models, Biological
  • Mutation
  • Optic Atrophy, Hereditary, Leber / drug therapy
  • Optic Atrophy, Hereditary, Leber / genetics*
  • Optic Atrophy, Hereditary, Leber / metabolism
  • Optic Atrophy, Hereditary, Leber / pathology
  • Retinal Ganglion Cells / metabolism*
  • Retinal Ganglion Cells / pathology


  • DNA, Mitochondrial