Background: Optic neuritis is experienced by a majority of multiple sclerosis (MS) patients and is typically characterized by episodes of acute, monocular vision loss. These inflammatory episodes can lead to damage or degeneration of the retinal ganglion cells (RGCs) comprising the optic nerve (ON). Experimental autoimmune encephalomyelitis (EAE) is a well-established model of MS in which mice are immunized to produce a neuro-autoimmunity that recapitulates the cardinal hallmarks of the human disease, namely, increased oxidative stress, demyelination, and neurodegeneration.
Objective: It has been previously demonstrated that mice deficient for the master anti-oxidant transcription factor Nrf2 are more susceptible to the motor deficits and spinal cord pathology induced by EAE. The goal of this study was to determine if Nrf2-deficient mice also exhibited exacerbated visual pathology in EAE.
Materials and Methods: EAE was induced in 8-week-old wildtype (WT) and Nrf2 knockout (KO) mice via immunization against MOG antigen. Visual acuity via optokinetic tracking (OKT) and motor deficits were assessed daily. Mice were harvested 21 days post-immunization. Retinas were flatmounted, immunostained, and RGCs were counted. ONs were paraffin-embedded and stained with H&E or immune cell-specific antibodies.
Results: Nrf2 KO mice exhibited more severe motor deficits, OKT decreases, RGC loss, and ON inflammation in response to EAE. This was not due to global differences in immune system development relative to WT mice.
Conclusion: Nrf2 plays a neuroprotective role in EAE-associated optic neuritis and may be an optimal therapeutic target to prevent RGC degeneration that leads to permanent visual impairment in MS patients.
© 2015 Published by Elsevier Inc.