Leber hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA (mtDNA) disorder with the majority of patients harboring one of three primary mtDNA point mutations, namely, m.3460G>A (MTND1), m.11778G>A (MTND4), and m.14484T>C (MTND6). LHON is characterized by bilateral subacute loss of vision due to the preferential loss of retinal ganglion cells (RGCs) within the inner retina, resulting in optic nerve degeneration. This review describes the clinical features associated with mtDNA LHON mutations and recent insights gained into the disease mechanisms contributing to RGC loss in this mitochondrial disorder. Although treatment options remain limited, LHON research has now entered an active translational phase with ongoing clinical trials, including gene therapy to correct the underlying pathogenic mtDNA mutation.
Keywords: Gene therapy; Haplogroup; Heteroplasmy; LHON; Mitochondrial disease; Optic neuropathy.
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