Title:Genetic Basis of Mitochondrial Optic Neuropathies
Volume: 14
Issue: 8
Author(s): A. Maresca, L. Caporali, D. Strobbe, C. Zanna, D. Malavolta, C. La Morgia, M.L. Valentino and V. Carelli
Affiliation:
Keywords:
DOA, environmental triggers, genetic modifiers, LHON, mitochondrial biogenesis, mitochondrial DNA,
OPA1, optic neuropathies.
Abstract: Over two decades have elapsed since the first mtDNA point mutation was associated with Leber’s
hereditary optic neuropathy (LHON) in 1988. We have subsequently witnessed a substantial understanding of
the molecular basis of hereditary optic neuropathies, as well as of their clinical features and pathogenic
mechanisms. It became clear that the large majority of genetic optic neuropathies have a primary or an indirect
involvement of mitochondrial functions, justifying the definition of “mitochondrial optic neuropathies”. Despite
this progress many unsolved features remain to be understood, such as incomplete penetrance and variable
clinical expressivity in LHON and dominant optic atrophy (DOA), gender prevalence in LHON, and complex
gene/environment interactions in both LHON and DOA. The most recent advancement in our understanding of
the molecular basis of mitochondrial optic neuropathies is the topic of this review. In particular, we analyze the
role that mitochondrial biogenesis may play in the compensatory mechanisms that underlie incomplete
penetrance and clinical expressivity, a scenario relevant for the possible design of future therapeutic
approaches.