Related Experiment Video
Updated: Jul 9, 2026
A Surgical Approach for Optic Nerve Crush in a Rabbit Model
Published on: July 8, 2025
Long-term suppression of neurodegeneration in chronic experimental optic neuritis: antioxidant gene therapy
Xiaoping Qi1, Liang Sun, Alfred S Lewin
1Department of Ophthalmology, University of Florida, College of Medicine, Gainesville, FL 32610-0284, USA.
Purpose:
To test in mice with experimental autoimmune encephalomyelitis (EAE) a strategy designed to treat patients at risk for axonal degeneration and persistent visual loss from optic neuritis and multiple sclerosis.
Methods:
The authors cloned the human extracellular superoxide dismutase (ECSOD) or catalase (CAT) gene into recombinant adenoassociated virus (AAV). Transgene expression was evaluated by immunochemistry of infected RGC-5 cells and after intravitreal injection of AAV-ECSOD or AAV-CAT, or both, into the right eyes of DBA/1J mice. Control cells and left eyes were inoculated with AAV-GFP. Animals were sensitized for EAE, followed by serial contrast-enhanced MRI for 6 months, and then were euthanatized. The effects of ECSOD and CAT modulation on the EAE optic nerve were gauged by computerized analysis of optic nerve volume, myelin fiber area, axonal cell loss, and retinal ganglion cell (RGC) loss.
Results:
Western blot analysis of infected RGC-5 cells revealed that expression of ECSOD increased 15-fold and that of CAT increased 3.5-fold. One month after intraocular injections, transgene expression increased 4-fold for AAV-ECSOD and 3.3-fold for AAV-CAT. Six months after intraocular injections and EAE sensitization, combination therapy with ECSOD and catalase decreased RGC loss by 29%, optic nerve demyelination by 36%, axonal loss by 44%, and cellular infiltration by 34% compared with the contralateral control eyes inoculated with AAV-GFP. Compared with the normal optic nerve, it limited RGC loss to 9%.
Conclusions:
Viral-mediated delivery of antioxidant genes provides long-lasting suppression against neuronal and axonal loss associated with permanent visual disability in patients with optic neuritis and multiple sclerosis.
Insights
Gene therapy using antioxidant genes, extracellular superoxide dismutase (ECSOD) and catalase (CAT), protected against vision loss in mice with experimental autoimmune encephalomyelitis (EAE). This approach reduced neuronal and axonal damage, offering potential for treating multiple sclerosis and optic neuritis.
Area of Science:
- Neuroscience
- Ophthalmology
- Gene Therapy
Background:
- Optic neuritis and multiple sclerosis can cause axonal degeneration and persistent visual loss.
- Experimental autoimmune encephalomyelitis (EAE) in mice serves as a model for these conditions.
- Developing effective treatments to prevent neuronal and axonal loss is crucial.
Purpose of the Study:
- To evaluate a gene therapy strategy using recombinant adenoassociated virus (AAV) vectors to deliver antioxidant genes (ECSOD and CAT) in a mouse model of EAE.
- To assess the protective effects of ECSOD and CAT on optic nerve damage and retinal ganglion cell (RGC) loss.
Main Methods:
- Human ECSOD and CAT genes were cloned into AAV vectors.
- AAV vectors carrying ECSOD, CAT, or GFP (control) were injected intravitreally into DBA/1J mice.
- Mice were sensitized to induce EAE and monitored for 6 months using MRI.
- Optic nerve and retinal tissues were analyzed for volume, myelin, axonal loss, and RGC loss.
Main Results:
- Intraocular AAV-ECSOD and AAV-CAT demonstrated successful transgene expression.
- Combination therapy with ECSOD and CAT significantly reduced RGC loss (29%), demyelination (36%), axonal loss (44%), and cellular infiltration (34%) compared to controls.
- The treatment limited RGC loss to 9% compared to normal optic nerves.
Conclusions:
- Viral-mediated delivery of antioxidant genes (ECSOD and CAT) offers long-lasting neuroprotection.
- This gene therapy strategy shows promise for preventing neuronal and axonal loss in conditions like optic neuritis and multiple sclerosis.
- The findings support the potential of antioxidant gene therapy for preserving vision in patients at risk of visual disability.
