Exploring mito-nuclear genetic factors in Leber’s hereditary optic neuropathy: insights from comprehensive profiling of unique cases
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial complex I disorder and causes inexorable painless vision loss. Recent studies from India reported that a significant proportion of LHON patients lack primary mitochondrial DNA mutations, suggesting that alternative genetic factors contribute to disease development. Therefore, this study investigated the genetic profile of LHON-affected individuals in order to understand the role of mito-nuclear genetic factors in LHON. A total of…
Leber’s hereditary optic neuropathy: Update on the novel genes and therapeutic options
A maternal inheritance disorder called Leber’s hereditary optic neuropathy (LHON) is the most common primary mitochondrial DNA disorder. In most studies, there are more male patients than female patients, which contradicts the usual pattern in mitochondrial hereditary diseases. This suggests that nuclear DNA (nDNA) may influence the degeneration of retinal ganglion cells (RGCs) in LHON. The primary cause of this is dysfunction in complex I of the electron transport chain, leading to ineffective…
HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber’s Hereditary Optic Neuropathy-like Models In Vitro and In Vivo
CONCLUSION: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.
Mutation at the entrance of the quinone cavity severely disrupts quinone binding in respiratory complex I
In all resolved structures of complex I, there exists a tunnel-like Q-chamber for ubiquinone binding and reduction. The entrance to the Q-chamber in ND1 subunit forms a narrow bottleneck, which is rather tight and requires thermal conformational changes for ubiquinone to get in and out of the binding chamber. The substitution of alanine with threonine at the bottleneck (AlaThr MUT), associated with 3460/ND1 mtDNA mutation in human complex I, is implicated in Leber’s Hereditary Optic Neuropathy…
Choriocapillaris and choroidal thickness in all Leber hereditary optic neuropathy stages using swept source technology
CONCLUSION: The CC VD remained stable across the LHON stages. Choroidal vasculature does not appear to play a role in LHON pathophysiology. Further research is needed on ChT as a potential biomarker of LHON.
Progress in diagnosis and treatment of Leber’s hereditary optic neuropathy
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial genetic disease with central vision loss as the main symptom. It is one of the diseases that cause vision loss and optic atrophy in young and middle-aged people. The mutations of these three primary mitochondrial mutations, m.11778G>A, m.14484T>C, and m.3460G>A, are the main molecular basis, but their pathogenesis is also affected by nuclear genes, mitochondrial genetic background, and environmental factors. This article summarizes…
Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis
CONCLUSIONS: AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.
COVID-19 Disease: A Trigger for Leber Hereditary Optic Neuropathy (LHON)
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Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects With Leber’s Hereditary Optic Neuropathy: A Randomized Trial
CONCLUSIONS: Elamipretide treatment was generally well tolerated with no serious adverse events reported. Although this study did not meet its primary BCVA efficacy endpoint, improvements across assessments on visual function during the OLE, and the post-hoc findings of the HVF central region, were encouraging and require further exploration.
Leber’s Hereditary Optic Neuropathy (LHON): Clinical Experience and Outcomes after Long-Term Idebenone Treatment
CONCLUSIONS: Our study demonstrated positive results with long-term Idebenone use. Contrary to medical literature, our female patient had a favorable evolution, despite the delayed diagnosis.