Related Experiment Video
Updated: Aug 12, 2026
10:50
Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
8.4K
Complex I subunit gene therapy with NDUFA6 ameliorates neurodegeneration in EAE
Venu Talla1, Rajeshwari Koilkonda1, Vittorio Porciatti1
1Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States.
Investigative Ophthalmology & Visual Science
|January 24, 2015
Summary
Gene therapy using NDUFA6Flag successfully treated mitochondrial dysfunction in an experimental autoimmune encephalomyelitis (EAE) model. This approach rescued vision and reduced neurodegeneration, offering potential for optic neuritis and multiple sclerosis (MS) patients.
Area of Science:
- Neuroscience
- Ophthalmology
- Genetics
- Mitochondrial Biology
Background:
- Mitochondrial dysfunction is a key factor in permanent disability caused by experimental autoimmune encephalomyelitis (EAE).
- Restoring mitochondrial function may offer a therapeutic strategy for neurodegenerative conditions affecting vision.
Purpose of the Study:
- To investigate the potential of NDUFA6 gene therapy to counteract mitochondrial dysfunction and neurodegeneration in EAE.
- To evaluate the impact of NDUFA6 gene therapy on visual function and retinal structure in an EAE model.
Main Methods:
- Adeno-associated viral vector serotype 2 carrying the NDUFA6 gene (scAAV-NDUFA6Flag) was administered intravitreally to EAE-sensitized mice.
- Visual function and retinal structure were assessed using pattern electroretinograms (PERGs) and optical coherence tomography (OCT).
- Histopathology, apoptosis assays, and complex I activity measurements were performed to evaluate treatment efficacy.
Main Results:
- NDUFA6Flag overexpression successfully integrated into complex I and restored retinal complex I activity in EAE mice.
- Gene therapy significantly reduced axonal loss (73%), retinal ganglion cell (RGC) loss (88%), and RGC apoptosis (66%).
- Treatment prevented vision loss, as evidenced by preserved PERG amplitudes compared to untreated EAE mice.
Conclusions:
- NDUFA6 gene therapy effectively suppressed neurodegeneration and ameliorated mitochondrial dysfunction in the EAE model.
- These findings suggest that NDUFA6 gene therapy could be a promising treatment for optic neuritis and multiple sclerosis (MS) patients experiencing vision loss due to mitochondrial dysfunction.
