Category: LHON

Leber hereditary optic neuropathy: clinical picture and initial workup data

Leber hereditary optic neuropathy (LHON) is a rare mitochondrial disease, responsible for blindness by bilateral involvement of central vision. It usually affects young men but can occur at any age and in women. Its diagnosis is suspected on the family history and the initial clinical picture, and the definitive diagnosis of LHON is obtained by genetic testing and the molecular identification of the mitochondrial genetic point mutation. The initial workup should include an assessment of visual…

Medical treatments in Leber’s hereditary optic neuropathy

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disease caused by a mutation of mitochondrial DNA. LHON targets retinal ganglion cells (RGC), whose axons form the optic nerve. The mutation that leads to LHON is silent until an unknown trigger causes dysfunction of complex I in the mitochondria of RGC. This results in discontinuation of RGC energy production and, eventually, RGC apoptosis. Patients experience bilateral sequential central scotoma over the course of a few…

Leber hereditary optic neuropathy: update on genetics and pathomechanisms

Leber Hereditary Optic Neuropathy is still a dramatic disease of optic nerve. Origins and mechanisms are extensively studied in the last decades, in link with emergent therapeutic approaches. This article is an update on genetics and pathophysiology of LHON and leber-like inherited optic neuropathies.

Magnetic resonance imaging negative myelopathy in Leber’s hereditary optic neuropathy: a case report

CONCLUSIONS: The patient case demonstrates that myelopathy associated with LHON can present without abnormal findings in central nervous system MR imaging or in the CSF, and without evidence suggestive of multiple sclerosis or MS-like disease. The dorsal column seems to be particularly vulnerable to myelopathy changes in LHON. Evoked potential investigations may assist in confirming the diagnosis, when clinical features are in line with myelopathy but findings in CSF analysis and central nervous…

Neuroimaging in Leber Hereditary Optic Neuropathy: State-of-the-art and future prospects

Leber Hereditary Optic Neuropathy (LHON) is an inherited mitochondrial retinal disease that causes the degeneration of retinal ganglion cells and leads to drastic loss of visual function. In the last decades, there has been a growing interest in using Magnetic Resonance Imaging (MRI) to better understand mechanisms of LHON beyond the retina. This is partially due to the emergence of gene-therapies for retinal diseases, and the accompanying expanded need for reliably quantifying and monitoring…

Optic Nerve Structural and Functional Changes in LHON-Affected and Asymptomatic Maternal Relatives: Association with H and HV Mitochondrial Haplogroups

Leber Hereditary Optic Neuropathy (LHON) affects a minority of carriers of causative mitochondrial DNA mutations. We investigated a cohort of patients with LHON, including m.11778G>A, m.3460G>A, m.14484T>C and DNAJC30 c.152A>G variants, and their asymptomatic maternal carrier relatives for additional potential associations with vision loss. We assessed visual acuity, optical coherence tomography (OCT) of the peripapillary retinal nerve fibre layer (RNFL), visually evoked potential…

Nuclear modifier YARS2 allele correction restored retinal ganglion cells-specific deficiencies in Leber’s hereditary optic neuropathy

Leber’s hereditary optic neuropathy (LHON) is a maternally transmitted eye disease due to the degeneration of retinal ganglion cells (RGC). Mitochondrial 11778G > A mutation is the most common LHON-associated mitochondrial DNA (mtDNA) mutation. Our recent studies demonstrated some LHON families manifested by synergic interaction between m.11778G > A mutation and YARS2 allele (c.572G > T, p.Gly191Val) encoding mitochondrial tyrosyl-tRNA synthetase. However, the RGC-specific effects of…