Treatment of Leber Hereditary Optic Neuropathy

Abstract

Leber hereditary optic neuropathy (LHON) is a primary mitochondrial DNA (mtDNA) disorder characterised by bilateral, painless, subacute, central visual loss. The majority of patients harbour one of three mtDNA point mutations (m.3460G>A, m.11778G>A and m.14484T>C) with the m.11778G>A mutation being the most common cause of LHON worldwide. This mitochondrial optic neuropathy is characterised by the preferential early loss of retinal ganglion cells (RGCs) within the papillomacular bundle, which accounts for the dense central or caecocentral scotoma observed in this disorder. The management of LHON remains largely supportive, but rapid advances in drug discovery and genetic engineering are paving the way for more targeted strategies aimed at rescuing RGCs and improving the visual prognosis. Although a number of ethical and scientific concerns have been raised that need to be addressed further, mitochondrial replacement therapy offers the hope of preventing the maternal transmission of mtDNA LHON mutations for female carriers of childbearing age who wish to have their own biological children.