ReviewInvestigating Leber's hereditary optic neuropathy: Cell models and future perspectives

•LHON is the most common mitochondrial disease.•The tissue affected in LHON (optic nerve) is not available for testing.•Lymphoblasts, fibroblasts and cybrids are the most common models to study LHON.•Different approaches to study LHON are discussed.

Leber's hereditary optic neuropathy (LHON) was the first human disease found to be associated with a mitochondrial DNA (mtDNA) point mutation. The most common LHON mutations are 11778G > A, 3460G > A or 14484T > C. The most common clinical features of LHON are optic nerve and retina atrophy. The affected tissue is not available for studies, therefore a variety of other cell types are used. However, all models face difficulties and limitations in mitochondrial disease research. The advantages and disadvantages of different cell models used to study LHON, recent advances in animal model generation and novel approaches in this field are discussed.