Late-onset Leber Hereditary Optic Neuropathy: disease triggers and prognostic factors in a large Italian cohort
CONCLUSIONS: Late-onset LHON represents a clinically relevant subset in which environmental and hormonal factors may contribute to disease conversion. In this retrospective cohort, high-dose idebenone treatment was associated with a higher probability of visual recovery, particularly among patients with a J or T haplogroup background. These exploratory findings should be considered hypothesis-generating and warrant confirmation in prospective studies.
Leber’s hereditary optic nerve atrophy
This review is devoted to Leber’s hereditary optic neuropathy (LHON), a rare maternally inherited ophthalmic disorder presenting as optic nerve atrophy and associated with an unfavorable prognosis. LHON is the most common primary mitochondrial DNA disorder, and most patients (more than 90% of cases) carry one of three point mutations. The 11778G>A mutation in the MT-ND4 gene is the most common worldwide and causes the most severe variant of the disease. LHON typically manifests as bilateral,…
Disease-mutations perturb proton transfer reactions in respiratory complex I
Respiratory Complex I powers oxidative phosphorylation by a long-range proton-coupled electron transfer (PCET) reaction, with mutations linked to more than half of all human mitochondrial disorders. Yet, the molecular principles underlying the functional impairment remain difficult to test, as most mutations impede both the proton pumping and oxidoreductase activities due to the tightly coupled PCET process. Here, we probe how key disease mutations in the terminal ND5 subunit (NuoL/Nqo12),…
Reframing spaceflight-associated neuro-ocular syndrome as spaceflight-associated optic neuropathy (SAON): Transcriptomic in-vivo analysis reveals mitochondrial retinal ganglion cell injury during spaceflight
Spaceflight-Associated Neuro-Ocular Syndrome (SANS) has remained poorly understood throughout the history of human spaceflight despite being classified as the largest physiologic barrier that astronauts face. Existing mechanistic explanations of SANS are limited in accounting for its tissue specificity, interindividual heterogeneity, and persistence beyond return to Earth, which has left countermeasure development without a coherent biological target. Through integration of tissue-resolved…
Acute-phase characteristics of RNFL thickness in older patients with Leber hereditary optic neuropathy: a single-center retrospective OCT study
CONCLUSION: Acute-phase RNFL thickening may be less prominent with increasing age in m.11778G > A LHON, particularly in patients aged ≥ 50 years. LHON should not be excluded solely because RNFL thickening is inconspicuous in older-onset cases.
Progressive mitochondrial and autophagic dysfunction during RGC development driven by a LHON-associated mitochondrial tRNA(Thr) mutation
Leber’s hereditary optic neuropathy (LHON) is a genetically inherited disease of the eye triggered by mtDNA mutations, leading to degeneration of RGCs. We previously reported that the mitochondrial tRNA^(Thr) (MT-TT) 15927G > A homoplasmic mutation disrupted the base pairing (28C-42G) conserved in the anticodon stem of tRNA^(Thr), impairing t⁶A modification, aminoacylation, and steady-state tRNA^(Thr) levels, ultimately resulting in mitochondrial dysfunction. However, the absence of suitable…
Systematic review of Leber’s hereditary optic neuropathy – Clinical diagnosis, genetics overview and current concepts of treatment
Leber hereditary optic neuropathy (LHON) is the most common mitochondrial disorder, typically causing substantial, often permanent, central vision loss in young adults. It manifests as a subacute optic neuropathy, frequently progressing sequentially in both eyes, due to selective degeneration of retinal ganglion cells (RGCs). The condition is primarily associated with three mitochondrial DNA (mtDNA) point mutations-m.11778G>A, m.14484T>C, and m.3460G>A-located in complex I of the mitochondrial…
When LHON Mimics Demyelination: Area Postrema Syndrome in Biallelic DNAJC30 Variants
Introduction: Biallelic pathogenic variants in DNAJC30 cause an autosomal recessive form of Leber hereditary optic neuropathy (LHONAR1), traditionally considered a mitochondrially transmitted disorder. The phenotypic spectrum of diseases linked to DNAJC30 includes isolated optic neuropathy, Leigh syndrome spectrum (LSS), and atypical LHON-plus. Case description: Here, we report a 13-year-old boy presenting symptoms of area postrema syndrome (APS), with recurrent vomiting, vertigo, nystagmus, and…
Late-Onset Leber Hereditary Optic Neuropathy: A Report of a Case and Review of the Literature
Leber hereditary optic neuropathy (LHON) constitutes a mitochondrial disorder characterized by subacute, bilateral central vision impairment, secondary to mitochondrial DNA (mtDNA) mutations. These mutations compromise Complex I, subsequently precipitating the degeneration of retinal ganglion cells (RGCs). While traditionally manifesting in young males, contemporary literature has documented a small number of cases of late-onset presentation. Numerous studies have suggested the existence of a…
Archetypal Visual Field Analysis of Patients With Chronic Leber Hereditary Optic Neuropathy in Relation to Visual Recovery
CONCLUSIONS: AA is a robust method for categorizing and quantifying VF damage in patients with chronic LHON, providing novel insights into the complexity of the disease. The findings suggest that the recovery of VA and VF damage are not transposable, although not entirely independent either, and that both parameters should be considered in the comprehensive assessment of functional recovery in LHON.