Genetically silencing the transcription factor Nrf2 causes visual impairment, optic nerve inflammation, and retinal ganglion cell (RGC) degeneration in a mouse model of multiple sclerosis (MS), according to a study published in the scientific journal Molecular Vision. The finding suggests Nrf2 could protect against optic neuritis (inflammation of the optic nerve), which is a complication often associated with MS.
Results also suggest that the approved MS treatment Tecfidera (dimethyl fumarate [DMF]), which activates the Nrf2 antioxidant pathway, may be helpful in limiting MS patients’ vision problems, according to the authors of the study, “Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis.”
The team of researchers, led by Scott Plafker, PhD, associate member of the Aging & Metabolism Research Program at the Oklahoma Medical Research Foundation, immunized normal mice and mice lacking Nrf2 to produce neuro-autoimmunity that mimics characteristics of MS, including inflammation, and neurodegeneration of the brain, spinal cord, and optic nerve. They then assessed the animals’ ability to move and their visual acuity for 21 days.
Female MS mice lacking Nrf2 had more severe motor problems than those with Nrf2. Visual acuity deficits, optic nerve inflammation, and RGC degeneration were more pronounced in both genders of MS mice that lacked Nrf2, compared to control MS mice.
Visual deficits were noticed — and seen to worsen — in one eye of each mouse, which is similar to what MS patients experience.
Nrf2 is a key transcription factor that regulates the oxidative stress response. Oxidative stress associated with inflammation was known to play a key role in spinal cord damage, but its role in optic nerve inflammation and vision problems had not been studied.
The findings “suggest that the recently approved MS treatment, DMF, may have clinical efficacy in limiting visual pathologies for patients,” the researchers wrote.
The U.S. Food and Drug Administration (FDA) approved Tecfidera capsules in 2013 to treat adults with relapsing forms of MS.