Abstract
Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber’s hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated.
Highlights
Hereditary optic neuropathies are a heterogeneous group of diseases, which may be either an isolated optic neuropathy or optic neuropathy in the context of a more complex multi-systemic disease
Additional loci have been identified in X-linked (OPA2) [25] and recessive (OPA6 and OPA7 ) hereditary optic neuropathies, the latter recently associated with mutations in TMEM126A [26, 27]
As for Leber’s hereditary optic neuropathy (LHON), the clinical examination in dominant optic atrophy (DOA) demonstrates the maintenance of the pupillary light reflex
Summary
Hereditary optic neuropathies are a heterogeneous group of diseases, which may be either an isolated optic neuropathy or optic neuropathy in the context of a more complex multi-systemic disease. GENETIC BASIS OF ISOLATED OPTIC NEUROPATHIES Leber’s hereditary optic neuropathy is a maternally inherited disorder and in 90–95% of cases it is due to one of three mitochondrial DNA (mtDNA) mutations In about 70% of cases, is due to mutations in the OPA1 gene.
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