Purpose of review: We review the recent advances in animal models generated to study the complexities of mitochondrial optic neuropathies and the therapeutic strategies proposed for these disorders.
Recent findings: We have recently witnessed a rapid proliferation of animal models attempting to recapitulate the clinical and pathogenic features of human genetic mitochondrial optic neuropathies, that is Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). Although the generation of an animal model of disorders due to nuclear gene defects is well established and technically feasible, for mitochondrial DNA (mtDNA)-based diseases, there have been major limitations. Notwithstanding these difficulties, various approaches circumvented the problem by proposing biochemical or tissue-specific delivery models of mutant mtDNA able to induce retinal ganglion cell disease, contextually providing gene therapy solutions. Recently, the first mito-mice model of LHON has also been reported. In addition to gene therapy, new generation quinone-derived molecules and other strategies based on pharmacological activation of mitochondrial biogenesis are currently being tested, with the first clinical trials being initiated in humans.
Summary: Major advancements have been achieved in delivering mtDNA to mitochondria and generating faithful animal models of mtDNA-based optic neuropathy. The availability of these approaches, including animal models of nuclear-encoded optic neuropathies, provides unprecedented opportunities to test therapies, both genetic and pharmacological, paving the road to clinical trials in humans.