Scientists who genetically silenced the transcription factor Nrf2 in a study of mice found it caused visual impairment and retinal ganglion cell (RGC) degeneration in MS.
The study, published in scientific journal Molecular Vision, was undertaken to determine the consequences of Nrf2 loss for Experimental Autoimmune Encephalomyelitis (EAE) optic neuritis and visual function.
Researchers found that Nrf2 could protect against optic neuritis (inflammation of the optic nerve), which is often a complication associated with MS.
The results also suggested that Tecfidera (dimethyl fumarate), which is an approved MS treatment, activates the Nrf2 antioxidant pathway and according to the study’s authors could be helpful in limiting MS patients’ vision problems. They said: “Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis.”
Researchers immunised normal mice and mice lacking Nrf2 to produce neuro-autoimmunity that mimics characteristics of MS, such as inflammation and neurodegeneration of the brain, spinal cord and optic nerve. Over a period of 21 days they monitored the animals’ ability to move and their vision.
Although the sharpness of their vision was failing, optic nerve inflammation and RGC degeneration were more pronounced in both male and female MS mice that lacked Nrf2, compared to immunised normal mice. Females lacking Nrf2 had more severe motor problems than those with Nrf2.
Similarly to MS patients, the mice experienced more of a significant decrease in visibility in one eye.
Nrf2 is a transcription factor that in humans is encoded by the NFE2L2 gene. It regulates the oxidative stress response, which is associated with inflammation and is known to play a key role in spinal cord damage. However its role in optic nerve inflammation and vision problems had not, until now, been studied.
Researchers concluded that the findings suggest that the recently approved MS treatment, Tecfidera, may have clinical efficacy in limiting visual pathologies for patients.
Source: MS-UK (19/01/17)