B cell-dependent EAE induces visual deficits in the mouse with similarities to human autoimmune demyelinating diseases

• Published in: Journal of neuroinflammation Vol. 19; no. 1; pp. 54 - 17
• Main Authors: Joly, Sandrine, Mdzomba, Julius Baya, Rodriguez, Léa, Morin, Françoise, Vallières, Luc, Pernet, Vincent
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23.02.2022; BMC
• Subjects: Animals; B cells; Comparative analysis; Complications and side effects; Demyelinating diseases; Electroretinogram; Electroretinography; Encephalomyelitis; Encephalomyelitis, Autoimmune, Experimental - pathology; Experimental autoimmune encephalomyelitis; Health aspects; Humans; Inflammation; Methods; Mice; Mice, Inbred C57BL; Multiple sclerosis; Myelin-Oligodendrocyte Glycoprotein; Optic Nerve - pathology; Optic neuritis; Retinal diseases; Risk factors; Canada; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Inflammation; B cells; Electroretinogram; Optic neuritis
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-022-02416-y

In the field of autoimmune demyelinating diseases, visual impairments have extensively been studied using the experimental autoimmune encephalomyelitis (EAE) mouse model, which is classically induced by immunization with myelin oligodendrocyte glycoprotein peptide (MOG ). However, this model does not involve B cells like its human analogs. New antigens have thus been developed to induce a B cell-dependent form of EAE that better mimics human diseases. The present study aimed to characterize the visual symptoms of EAE induced with such an antigen called bMOG. After the induction of EAE with bMOG in C57BL/6J mice, visual function changes were studied by electroretinography and optomotor acuity tests. Motor deficits were assessed in parallel with a standard clinical scoring method. Histological examinations and Western blot analyses allowed to follow retinal neuron survival, gliosis, microglia activation, opsin photopigment expression in photoreceptors and optic nerve demyelination. Disease effects on retinal gene expression were established by RNA sequencing. We observed that bMOG EAE mice exhibited persistent loss of visual acuity, despite partial recovery of electroretinogram and motor functions. This loss was likely due to retinal inflammation, gliosis and synaptic impairments, as evidenced by histological and transcriptomic data. Further analysis suggests that the M-cone photoreceptor pathway was also affected. Therefore, by documenting visual changes induced by bMOG and showing similarities to those seen in diseases such as multiple sclerosis and neuromyelitis optica, this study offers a new approach to test protective or restorative ophthalmic treatments.