Advances in research on Leber's hereditary optic neuropathy

Leber's hereditary optic neuropathy (LHON) is the most prevalent primary mitochondrial DNA (mtDNA) disorder, and the majority of patients carry one of three primary mtDNA point mutations, specifically MTND1-3460, MTND4-11778, and MTND6-14484. LHON is characterized by bilateral subacute vision loss, primarily caused by the selective degeneration of retinal ganglion cells (RGCs) in the inner retinal layer. This review outlines the clinical manifestations associated with mtDNA LHON mutations and provides recent insights into the underlying mechanisms that result in RGC loss in this mitochondrial disorder. Although treatment options are currently limited, with ongoing clinical trials, LHON research has now entered an active translational phase, aiming at rectifying pathogenic mtDNA mutations.