Mitochondrial DNA variants in a cohort from Argentina with suspected Leber’s hereditary optic neuropathy (LHON)
The present study investigates the spectrum and analysis of mitochondrial DNA (mtDNA) variants associated with Leber hereditary optic neuropathy (LHON) in an Argentinean cohort, analyzing 3 LHON-associated mitochondrial genes. In 32% of the cases, molecular confirmation of the diagnosis could be established, due to the identification of disease-causing variants. A total of 54 variants were observed in a cohort of 100 patients tested with direct sequencing analysis. The frequent causative…
Mitochondrial optic neuropathies
Mitochondrial optic neuropathies have a leading role in the field of mitochondrial medicine ever since 1988, when the first mutation in mitochondrial DNA was associated with Leber’s hereditary optic neuropathy (LHON). Autosomal dominant optic atrophy (DOA) was subsequently associated in 2000 with mutations in the nuclear DNA affecting the OPA1 gene. LHON and DOA are both characterized by selective neurodegeneration of retinal ganglion cells (RGCs) triggered by mitochondrial dysfunction. This is…
Considering Leber´s hereditary optic neuropathy
Leber´s hereditary optic neuropathy (LHON) disease is a mitochondriopathy characterized by dysfunction and later on degeneration of retinal ganglion cells, in particular those contributing to the papillomacular bundle, leading to optic atrophy. Being devoid of pathognomonic features clinical diagnosis is difficult, but LHON should be suspected in all patients presenting with a clinical picture of bilateral or painless optic neuritis, irrespective of age, and the diagnosis can be confirmed by…
Optimisation of AAV-NDI1 Significantly Enhances Its Therapeutic Value for Correcting Retinal Mitochondrial Dysfunction
AAV gene therapy for ocular disease has become a reality with the market authorisation of Luxturna^(TM) for RPE65-linked inherited retinal degenerations and many AAV gene therapies currently undergoing phase III clinical trials. Many ocular disorders have a mitochondrial involvement from primary mitochondrial disorders such as Leber hereditary optic neuropathy (LHON), predominantly due to mutations in genes encoding subunits of complex I, to Mendelian and multifactorial ocular conditions such as…