Progressive generalized dystonia caused by a mutation in the MT-ND6 gene
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Optic neuropathy arising from the synergy between YARS2 and mitochondrial COX1 mutations
Leber hereditary optic neuropathy (LHON) is a paradigm for mitochondrial retinopathy. Here, we investigate the mechanism underlying the interaction between nuclear modifier and mtDNA mutation(s) that manifests optic neuropathy in vivo to develop an effective therapeutic approach for this disease using mouse models bearing LHON-linked Yars2^(G186V) or COI^(V421A) mutation alone and double mutations. Yars2^(G186V) alters mitochondrial translation and assembly and activities of complex I, III, and…
Molecular Mechanism of Mitochondrial Complex I Disruption by m.14484T>C Underlying Leber Hereditary Optic Neuropathy
Leber’s Hereditary Optic Neuropathy (LHON) is a rare genetic condition and severe neurological disorder characterized by dysfunctional mitochondria under extreme oxidative stress, resulting in retinal ganglion cell death and subsequent rapid bilateral loss of central vision. The m.14484T>C mutation in the ND6 subunit of mitochondrial complex I is known for inducing LHON, and is a prevalent LHON-associated mutation, yet its mechanism of impairment at the molecular level is currently unresolved….
Pharmacological Depletion of Retinal Mononuclear Phagocytes Is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy
CONCLUSIONS: Pexidartinib effectively depletes retinal MNPs and is neuroprotective in the setting of severe RGC mitochondrial dysfunction. This therapeutic effect is additive to that of hypoxia. Combating retinal neuro-inflammation may therefore be a useful adjunct therapy in mitochondrial optic neuropathies like Leber hereditary optic neuropathy (LHON).
Oxidative Stress and Inflammatory Biomarkers in Aqueous Humor and Blood of Patients with Leber’s Hereditary Optic Neuropathy
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes visual impairment due to the degeneration of retinal ganglion cells. Oxidative stress (OS) and inflammatory cytokines have been implicated in its pathophysiology. We investigated, for the first time, the presence of OS biomarkers and inflammatory cytokines in the aqueous humor and peripheral blood of LHON patients compared to controls, aiming to identify potential clinical biomarkers for diagnosis and disease…
Leber Hereditary Optic Neuropathy-Associated Novel Mutation in MT-RNR2 Gene: A Case Report
CONCLUSION: MT-RNR2 gene mutation was the possible cause for LHON in this patient. Herein, we describe a novel mutation and associated clinical features. This case report also underscores the importance of considering LHON as a differential diagnosis for optic neuritis, even in a patient with an established MS.
Difference in pupillary response to red and blue color stimuli between glaucoma and Leber hereditary optic neuropathy patients with comparable central visual dysfunction
CONCLUSIONS: Compared with POAG patients who had comparable macular structural and functional damage, LHON patients showed better pupillary responses during blue light stimulation and PIPR, reflecting preserved ipRGC function.
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.