Amyotrophic Lateral Sclerosis With Concurrent LHON-associated m.14484T>C Mutation: A Case Report and Literature Review
CONCLUSION: We provide a case report and a literature review aimed at increasing the understanding of the connection between the two. It is essential to consider the potential modifying role of mitochondrial pathogenic genes in ALS.
Comparison of thickness changes in retinal nerve fibre layer in Leber’s hereditary optic neuropathy patients with 11778, 14484 and 3460 mutations
CONCLUSIONS: The papillomacular bundle was the initial and preferential site of involvement in LHON patients across all mutation types. The pattern of RNFL involvement was similar among the three mutations: temporal quadrant thinning occurred first, followed by the inferior and superior quadrants, and finally the nasal quadrant. Patients with G11778A and G3460A mutations exhibited earlier and more pronounced RNFL atrophy compared to those with T14484C mutations.
Atypical clinical and MRI features in Leber hereditary optic neuropathy: a case series of four patients
CONCLUSION: MRI abnormalities involving the optic pathway do not exclude LHON and may be present in atypical cases. LHON should be considered in all patients presenting with bilateral subacute visual loss, even when clinical or imaging features suggest alternative diagnoses.
Mitochondrial-Immune Overlap in Leber Hereditary Optic Neuropathy: A Case Report and Lessons Learned
Background and Clinical Significance: Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder characterized by acute or subacute bilateral central vision loss, typically in young males. Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are immune-mediated demyelinating diseases that may present with optic neuritis and myelitis. Although distinct in etiology, recent evidence suggests that mitochondrial dysfunction and neuroinflammation can overlap, giving…
Optic Atrophy Predominant WFS1 Disorder-A Case-Control Study
CONCLUSIONS: Our cohort of patients with WS1 showed uncharacteristically mild vision loss and minimal syndromic features, suggesting that a milder alternative phenotype with WFS1 mutations is possible in contrast to the traditional DIDMOAD syndrome. Compared with other OA syndromes, these patients with WS1 showed significant associations with arcuate visual field defects and trends toward superior/inferior peripapillary RNFL thinning. This suggests that relative preservation of papillomacular…
Serum neuronal, glial and mitochondrial markers in autosomal dominant optic atrophy and Leber hereditary optic neuropathy
Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (ADOA) are the two most prevailing primary mitochondrial optic neuropathies. Both diseases preferentially affect the smallest retinal ganglion cells (GCs) of the papillomacular bundle, causing central visual loss in young patients. Although ADOA and LHON show striking similarities, including the convergence of underlying pathologic mitochondrial mechanisms, they differ clinically. The major distinction lies in the…
Trans-generational maintenance of mitochondrial DNA integrity in oocytes during early folliculogenesis
Mutations in mitochondrial DNA (mtDNA) can lead to mitochondrial and cellular dysfunction. However, recent studies suggest that purifying selection acts against mutant mtDNAs during transgenerational transmission. We investigated the mtDNA dynamics during ovarian follicle development. Using base-editing, we generated mice harboring a 3177 G > A mutation corresponding to the human Leber hereditary optic neuropathy (LHON)-related mtDNA mutation and confirmed a transgenerational reduction of the…
Advanced therapies for inherited optic neuropathies
Inherited optic neuropathies (IONs), such as Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), typically lead to irreversible severe vision loss due to mitochondrial dysfunction causing retinal ganglion cell degeneration. Although current treatment options are limited, substantial progress has been made recently in our understanding of the molecular genetic pathways that lead to retinal ganglion cell loss. Clinical trials for LHON have demonstrated the…
Preclinical Assessment of Mitochondrial-Targeted ND4 Gene Therapy for Leber Hereditary Optic Neuropathy
CONCLUSIONS: Intravitreal delivery of MTSAAV/hND4 in rodents resulted in favorable biodistribution, with vector DNA largely confined to the injected eye and minimal systemic exposure. No vector-related adverse effects were observed based on functional, anatomic, and histopathological assessments, supporting the ocular safety of this gene therapy strategy. These findings provide preclinical evidence supporting the advancement of MTSAAV-mediated ND4 gene therapy toward clinical trials for LHON.
Metformin promotes mitochondrial integrity through AMPK-signaling in Leber’s hereditary optic neuropathy
Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder caused by mitochondrial DNA mutations in complex I of the respiratory chain, leading to impaired ATP production, mitochondrial fragmentation, and oxidative stress that contribute to vision loss. This study investigated the potential repurposing of metformin, a widely used antidiabetic drug, in fibroblasts from LHON patients carrying the m.11778G>A mutation. Fibroblasts from LHON patients and healthy individuals were…