Abstract
Purpose :
To study the visual impairments associated with multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) is a standard animal model induced by immunizing mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55). However, this form of EAE idoes not involve B cells, in contrast to MS. The present study aimed to characterize the visual symptoms in a B cell-dependent EAE to better mimic human MS.
Methods :
B cell-dependent EAE was induced with an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J male mice, changes in visual function were followed by electroretinography and optomotor acuity tests. Motor deficits were monitored in parallel with a standard clinical scoring method. Retinal neuron survival, gliosis, microglia activation, optic nerve demyelination and opsin expression were examined by histological and Western blot analyses. Gene expression changes were determined by RNA sequencing.
Results :
bMOG EAE mice showed persistent loss of visual acuity. In contrast, the electroretinogram (ERG) and the motor function spontaneously recovered after deficits culminating in the inflammatory disease phase. Visual acuity loss was associated with retinal inflammation, gliosis and synaptic impairments, as suggested by histological observations and transcriptomic results. Interestingly, chromatic ERG recordings revealed significant alterations in the M-cone pathway.
Conclusions :
The visual changes induced by bMOG in mice present similarities to those reported in multiple sclerosis and neuromyelitis optica. Therefore, bMOG EAE offers a new model to test experimental treatments for MS in the visual system.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.