LHON

PURPOSE: To assess changes in visual field (VF) values after gene therapy for Leber's hereditary optic neuropathy (LHON). METHODS: VF recovery, VF indices, and mean deviation in injected and uninjected eyes, before and after gene therapy, were examined in 2 groups of patients according to disease duration (≤2 years and > 2 years). Nine patients with LHON were treated by monocular intravitreal injection of AAV2-ND4. Finally, 7 patients were considered for subsequent comparisons; the first and second eyes were treated separately...

Mutations in mitochondrial DNA (mtDNA) have been associated with Leber's hereditary optic neuropathy (LHON) and their pathophysiology remains poorly understood. In this study, we demonstrated that a missense mutation (m.12338T>C, p.1M>T) in the ND5 gene contributed to the pathogenesis of LHON. The m.12338T>C mutation affected the first methionine (Met1) with a threonine and shortened two amino acids of ND5. We therefore hypothesized that the mutated ND5 perturbed the structure and function of complex I...

In this study, the authors present a sample of 71 patients with hereditary optic neuropathy and negative genetic test results for OPA1/OPA3/LHON. All of these patients later underwent genetic testing to rule out WFS. As a result, 53 patients (74.7%) were negative and 18 patients (25.3%) were positive for some type of mutation or variation in the WFS gene. The authors believe that this study is interesting because it shows that a sizeable percentage (25.3%) of patients with hereditary optic 25 neuropathy and negative genetic test results for OPA1/OPA3/LHON had WFS mutations or variants...

This report describes a 66-year-old Caucasian male who acutely developed severe, bilateral impairment of visual acuity at 24 years of age. Leber's hereditary optic neuropathy (LHON) was suspected but the diagnosis was not genetically confirmed until the age of 49 years when the primary LHON mutation m.3460G>A was detected. Since onset, visual acuity had slightly improved. The family history was positive for LHON (brother, two sisters of mother, female cousin) and genetically confirmed in his brother and one aunt...

OBJECTIVE: To assess quality of life (QoL) measures in Chinese Leber hereditary optic neuropathy (LHON) patients with the G11778A mutation. METHODS: Chinese LHON patients with the G11778A mutation were prospectively evaluated using the Visual Function Index (VF-14) at 6 months, 1 year, and 3 years after the involvement of the second eye. Patients who completed the VF-14 at all 3 follow-up time designations were included in the analysis. RESULTS: Fifty-five patients met the inclusion criteria...

Hereditary optic nerve disorders are rare. For ophthalmologists, Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are of particular relevance. LHON and ADOA are diseases of the retinal ganglion cells and are caused by mitchochondrial dysfunction. LHON is based on mutations of the mitochondrial, ADOA of the nuclear DNA. LHON is a disease that usually leads to severe visual impairment (visual acuity < 0.1). Since there is an approved therapy for LHON (Idebenone [Raxone]), the diagnosis has to be confirmed immediately by means of molecular genetic diagnostics...

There is growing evidence that the sequence variation of mitochondrial DNA (mtDNA), which clusters in population- and/or geographic-specific haplogroups, may result in functional effects that, in turn, become relevant in disease predisposition or protection, interaction with environmental factors and ultimately in modulating longevity. To unravel functional differences between mtDNA haplogroups we here employed transmitochondrial cytoplasmic hybrid cells (cybrids) grown in galactose medium, culture condition that force oxidative phosphorylation, and in the presence of rotenone, the classic inhibitor of respiratory Complex I...

Purpose: To present a report of longitudinal changes in radial peripapillary capillaries (RPC) and changes in retinal full thickness (RFT) and peripapillary retinal nerve fiber layer (RNFL) in a patient with Leber hereditary optic neuropathy (LHON). Observations: A 42-year-old man presented with acute- and presymptomatic-stage LHON in the left (OS) and right (OD) eyes, respectively, at the initial visit. Onset of LHON in the OD was observed 2 months after the initial visit...

Ethambutol is utilised in the treatment of Mycobacterium avium and Mycobacterium tuberculosis infection. The authors report two siblings who developed the adverse effect of ethambutol-induced optic chiasmopathy, with recovery following cessation of ethambutol. Discussion explores potential genetic predisposition to development of this condition and its resolution. Ethambutol optic neuropathy (EON), Leber's hereditary optic neuropathy (LHON), and other optic neuropathies of mitochondrial origin share a common pathophysiology...

BACKRGROUND: Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber's hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multicenter pilot study. Only LHON patients aged 18 years or more, with confirmed primary mitochondrial DNA mutations and strictly unilateral optic neuropathy occurring within 6 months prior to enrolment, were included in the study. All these patients, receiving treatment with oral cyclosporine (Neoral®, Novartis) at 2...

Mitochondrial function is closely linked to numerous aspects of eye health. Imbalance between the creation of energy and the development of reactive oxygen species (ROS) seems to be the cause of the development of mitochondrial dysfunctions. As a result of this energy deficit, the level of oxidative stress in the eye tissues increases, leading to numerous ophthalmic impairments. It is important to distinguish between primary mitochondrial eye diseases and secondary mitochondrial changes. Primary mitochondrial eye diseases, for example Leber's hereditary optic atrophy (LHON), retinitis pigmentosa and chronic progressive external ophthalmoplegia are caused by direct damage to mitochondrial function induced by defective genes, either located on mitochondrial DNA (mtDNA) or the DNA of the nucleus (nDNA)...

We here report on the existence of Leber's hereditary optic neuropathy (LHON) associated with peculiar combinations of individually non-pathogenic missense mitochondrial DNA (mtDNA) variants, affecting the MT-ND4, MT-ND4L and MT-ND6 subunit genes of Complex I. The pathogenic potential of these mtDNA haplotypes is supported by multiple evidences: first, the LHON phenotype is strictly inherited along the maternal line in one very large family; second, the combinations of mtDNA variants are unique to the two maternal lineages that are characterized by recurrence of LHON; third, the Complex I-dependent respiratory and oxidative phosphorylation defect is co-transferred from the proband's fibroblasts into the cybrid cell model...

Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease caused by homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. In this report, we generated an induced pluripotent stem cell (iPSCs) line, TVGH-iPSC-010-09, from the peripheral blood mononuclear cells of a female patient with Leber's hereditary optic neuropathy (LHON) by using the Sendai-virus delivery system. The resulting iPSCs retained the disease-causing mitochondrial DNA mutation, expressed pluripotent markers and could differentiate into the three germ layers...

The present study investigates the spectrum and incidence of mitochondrial DNA (mtDNA) mutations associated with Leber's hereditary optic neuropathy (LHON) in a Han population using a multi-gene panel with 46 LHON-associated mutations among 13 mitochondrial genes. A total of 23 mutations were observed in a cohort of 275 patients and 281 control subjects using multi-gene panel analysis. The causative mutations associated with LHON were identified to be m.11778G>A, m.14484T>C, m.3460 G>A, m.3635G>A, m...

BACKGROUND: Cardiac abnormalities have been described in patients with Leber hereditary optic neuropathy (LHON). Some are life-threatening because of the risk of ventricular fibrillation and sudden death. The purpose of our study was to better characterize the cardiac abnormalities in a large patient cohort with LHON. METHODS: A retrospective study of the electrocardiogram (EKG) results performed on all patients with LHON evaluated at The Reference Center for Rare Diseases in Ophthalmology, Paris, France, from January 2015 to June 2017...

Leber's hereditary optic neuropathy (LHON) is the maternally inherited mitochondrial disease caused by homoplasmic mutations in mitochondrial electron transport chain Complex I subunit genes. The mechanism of its incomplete penetrance is still largely unclear. In this study, we created the patient-specific human induced pluripotent stem cells (hiPSCs) from MT-ND4 mutated LHON-affected patient, asymptomatic mutation carrier and healthy control, and differentiated them into retinal ganglion cells (RGCs). We found the defective neurite outgrowth in affected RGCs, but not in the carrier RGCs which had significant expression of SNCG gene...

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