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…
In vivo mitochondrial base editing restores genotype and visual function in a mouse model of LHON
Leber hereditary optic neuropathy (LHON), a maternally inherited mitochondrial disorder, results from point mutations in mitochondrial DNA (mtDNA), primarily affecting the MT-ND4 gene. To date, no animal model harboring authentic LHON mutations has been available, limiting therapeutic development. However, when we attempted to generate such models using mitochondrial base editors, we found that activity-enhanced DddA11-based cytosine base editors (DdCBEs) induce off-target mtDNA mutations and…
Pathogenic mechanisms of Leber hereditary optic neuropathy caused by m.3472T>C mutation
CONCLUSIONS: The m.3472T>C mutation contributes to the pathogenesis of LHON by disrupting the structural stability of the ND1 subunit in complex Ⅰ, leading to mitochondrial dysfunction.
The Pedigree Study of Leber’s Hereditary Optic Neuropathy in Korean Population
CONCLUSIONS: This study expands previous research by offering new information on the penetrance of LHON in the Korean population through pedigree analysis.
From Castro to Quantum Mechanics: Marching Through Tunnels With Reactive Oxygen Species
The 2025 Jacobson Lecture revealed a scientific journey that began with the Cuban epidemic of blindness to recent studies of the quantum mechanical underpinnings of Leber’s Hereditary Optic Neuropathy (LHON). A sudden outbreak of bilaterally symmetrical optic neuropathy and peripheral neuropathy in more than 50,000 Cubans in 1993 had been blamed on a viral infection. Further investigations by our team revealed synergistic toxicity of folic acid deficiency and the consumption of homemade rum…
Super mitochondria-enriched extracellular vesicles enable enhanced mitochondria transfer
Mitochondria transfer is a spontaneous process that releases functional mitochondria to damaged cells via different mechanisms including extracellular vesicle containing mitochondria (EV-Mito) to restore mitochondrial functions. However, the limited EV-Mito yield makes it challenging to supply a sufficient quantity of functional mitochondria to damaged cells, hindering their application in mitochondrial diseases. Here, we show that the release of EV-Mito from mesenchymal stem cells (MSCs) is…
Navigating Health When Sudden Blindness Occurs: The Experience of Leber Hereditary Optic Neuropathy
Millions of Americans are affected by vision loss. Individuals diagnosed with Leber hereditary optic neuropathy face unique challenges due to the sudden and severe nature of vision loss. This genetic condition often results in difficulty obtaining a timely diagnosis and adjusting to blindness in a society primarily designed for sighted individuals. This study aimed to better understand the experiences of individuals who have severe central vision loss, particularly their interactions with the…
Development of Two In Vitro ND1-LHON Models for Evaluating Gene Therapy Efficacy
CONCLUSIONS: The study demonstrates the utility of transmitochondrial cybrids and iPSC-derived RGCs as reliable in vitro models for studying ND1-related LHON. The rAAV-ND1 gene therapy effectively restored mitochondrial function, highlighting its potential as a treatment for LHON caused by ND1 mutations. These findings underscore the value of in vitro systems for evaluating therapies when robust animal models are unavailable.
Hearing Impairments Are Not Uncommon in LHON Patients
No abstract
Chromatic pupil campimetry as objective diagnostic tool for progressive optic neuropathies
CONCLUSION: CPC effectively distinguished glaucoma and meningioma from healthy controls but was less reliable for differentiating ON subtypes. Our results indicate, that central pupillary escape is associated with inner retinal dysfunction.