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
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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.
Exploring rare mitochondrial DNA in Leber hereditary optic neuropathy
CONCLUSIONS: Our study probes into the clinical and genetic diversity of LHON with rare mtDNA mutations, revealing varied clinical presentations, such as more frequent unilateral involvement and enhanced optic nerve T2 MRI signals. Visual recovery was significantly better in the younger cohort. These results suggest the need for broader genetic testing in atypical LHON cases and offer insights into better prognostic strategies for new therapies.
Visual Recovery in Leber’s Hereditary Optic Neuropathy Plus: A Case Report and Literature Insight
CONCLUSION: This case underscores the importance of considering LHON plus in young patients with bilateral optic neuropathy and systemic features, particularly when the MT:14484C>T mutation is present, as early mitochondrial support can lead to favorable outcomes.
Efficacy and safety of intravitreal rAAV2-ND4 therapy for Leber’s hereditary optic neuropathy
CONCLUSION: This Phase 1/2 trial demonstrated no serious safety concerns among the 12 participants. And dose of 4.5 × 10⁹ vg, 0.05 mL was to be used in future Phase 3 study.
Establishment of human Leber’s hereditary optic neuropathy model using iPSC-derived retinal organoids
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease caused by mitochondrial DNA mutations, leading to central vision loss and retinal ganglion cell (RGC) degeneration. Progress in understanding LHON and developing treatments has been limited by the lack of human-like models. In this study, we aimed to establish a human retinal model of LHON using retinal organoids (ROs) from LHON patient-derived induced pluripotent stem cells (LHON-iPSCs). We first confirmed LHON-iPSCs were…