Electroretinographic oscillatory potentials in Leber hereditary optic neuropathy
CONCLUSIONS: Reduced OPs in LHON patients may represent disturbed neuronal interactions in the inner retina with preserved photoreceptoral (a-wave) to bipolar cell (b-wave) activation. Reduced DA OP2 and high-cutoff LA OP alterations may be further explored as functional measures to characterize LHON status and progression.
Prophylactic nicotinamide treatment protects from rotenone-induced neurodegeneration by increasing mitochondrial content and volume
Leber’s hereditary optic neuropathy (LHON) is driven by mtDNA mutations affecting Complex I presenting as progressive retinal ganglion cell dysfunction usually in the absence of extra-ophthalmic symptoms. There are no long-term neuroprotective agents for LHON. Oral nicotinamide provides a robust neuroprotective effect against mitochondrial and metabolic dysfunction in other retinal injuries. We explored the potential for nicotinamide to protect mitochondria in LHON by modelling the disease in…
Development of a deep learning model to distinguish the cause of optic disc atrophy using retinal fundus photography
The differential diagnosis for optic atrophy can be challenging and requires expensive, time-consuming ancillary testing to determine the cause. While Leber’s hereditary optic neuropathy (LHON) and optic neuritis (ON) are both clinically significant causes for optic atrophy, both relatively rare in the general population, contributing to limitations in obtaining large imaging datasets. This study therefore aims to develop a deep learning (DL) model based on small datasets that could distinguish…
Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial
Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N =…
Clinical Characteristics of m.11778G>A Leber Hereditary Optic Neuropathy with Favorable Outcomes
The prognosis of 11,778 mitochondrial mutations in Leber hereditary optic neuropathy (LHON) is poor. Patients with favorable outcomes (visual acuity better than 20/100) who could be observed for more than 6 months were analyzed. Among 74 patients (57 male, 17 female), 6 (8.1%) showed improvement in visual acuity of 20/100 or higher. The patients with favorable outcomes have better visual acuity at nadir (logMAR 0.98 ± 0.69 in the favorable patients and logMAR 2.32 ± 0.93 in the unfavorable…
A Japanese Case of Leber’s Hereditary Optic Neuropathy with the m.13051G>A Pathogenic Variant
Leber’s hereditary optic neuropathy (LHON) is one of the hereditary optic neuropathies and is principally caused by three frequent mitochondria deoxyribonucleic acid (DNA) pathogenic variants (m.11778 G>A, m.3460 G>A, and m.14484T>C). These pathogenic variants account for 90% of LHON cases, with rare pathogenic variants accounting for the remaining cases. We report the first Japanese case of LHON with the m.13051 G>A pathogenic variant, which is a rare primary pathogenic variant of LHON. A…
Variant and clinical landscape of Leber hereditary optic neuropathy based on 1516 families with mtDNA variants in a tertiary centre
CONCLUSION: Compared with non-East Asians, Chinese LHON patients had higher proportions of m.11778G>A and m.3635G>A and lower m.3460G>A mutations. A novel progression grade derived from optic disc category was proposed. The prognostic matrix indicated that lower grade and younger-onset age are the most favourable prognostic factors.
Dysregulation of the circRNA_0087207/miR-548c-3p/PLSR1-TGFB2 axis in Leber’s hereditary optic neuropathy in vitro
CONCLUSION: We showed that the downregulation of miR548c-3p plays a critical role in modulating cellular dysfunction and the apoptotic program of RGCs in LHON.
Genetic variants affecting NQO1 protein levels impact the efficacy of idebenone treatment in Leber hereditary optic neuropathy
Idebenone, the only approved treatment for Leber hereditary optic neuropathy (LHON), promotes recovery of visual function in up to 50% of patients, but we can neither predict nor understand the non-responders. Idebenone is reduced by the cytosolic NAD(P)H oxidoreductase I (NQO1) and directly shuttles electrons to respiratory complex III, bypassing complex I affected in LHON. We show here that two polymorphic variants drastically reduce NQO1 protein levels when homozygous or compound…
Epigenetic regulation of the nuclear genome associated with mitochondrial dysfunction in Leber’s hereditary optic neuropathy (LHON)
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial hereditary disease in which visual loss affects complex 1 activity of the electron transport chain of mitochondria. It first manifests as painless dulling or blurry in one or even both eyes, and as it develops, sharpness and color perception are lost. In addition to primary mitochondrial DNA (mtDNA) mutations, there are also other environmental and epigenetic factors involved in the pathogenesis of LHON. One of the most common…