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.
Health-related quality of life and tobacco and alcohol consumption in Leber hereditary optic neuropathy in Sweden
CONCLUSIONS: The HRQoL was similar among the Swedish LHON cohort compared to HC references. Swedish LHON cohort showed a higher prevalence of smoking. Snus usage, and harmful or hazardous alcohol consumption were higher among LHON affected individuals.
Diagnostic Yield and Clinical Impact of Comprehensive WES/WGS Testing Beyond Common Genetic Causes in Hereditary Optic Atrophy
Hereditary optic atrophy is characterized by degeneration of retinal ganglion cells and may result from a wide range of genetic etiologies. While pathogenic variants in OPA1 and primary mitochondrial variants causing Leber hereditary optic neuropathy (LHON) account for a substantial proportion of cases, many patients remain genetically unsolved. We evaluated the diagnostic yield and clinical impact of comprehensive whole exome/genome sequencing (WES/WGS)-based virtual panel testing in 62…
Analysis of genetic risk factors for Leber hereditary optic neuropathy in the Polish population
Leber hereditary optic neuropathy (LHON) is primarily caused by pathogenic mitochondrial DNA (mtDNA) variants, most commonly the m.11778G>A variant in the MT-ND4 gene. The presence of this variant alone is insufficient to trigger disease symptoms, of which vision loss is the hallmark. Given the incomplete penetrance and inter-population variability in modifying factors, this study aimed to investigate two previously proposed genetic risk factors for LHON in the Polish population. Using…