Abstract
BackgroundMultiple sclerosis (MS) is often accompanied by optic nerve inflammation. And some patients experience permanent vision loss. We examined if the grade of optic nerve infiltration and demyelination affects the severity of clinical signs in an experimental autoimmune encephalomyelitis (EAE) model. The loss of retinal ganglion cells (RGC) and alterations in glia activity were also investigated.MethodsC57BL/6 mice were immunized with peptide MOG35-55 in complete Freund’s adjuvant (CFA) and controls received PBS in CFA. Then 23 days post immunization eyes were prepared for flatmounts and stained with Nissl to evaluated neuronal density. Clinical EAE symptoms as well as cell infiltration and demyelination in the optic nerve were examined. Retinal sections were stained with hematoxylin and eosin and silver stain. Immunohistochemistry was used to label RGCs (Brn-3a), apoptotic cells (caspase 3), macroglia (glial fibrillary acidic protein (GFAP)), microglia (Iba1), macrophages (F 4/80) and interleukin-6 (IL-6) secretion.ResultsEAE symptoms started at day 8 and peaked at day 15. Cell infiltrations (P = 0.0047) and demyelination (P = 0.0018) of EAE nerves correlated with the clinical score (r > 0.8). EAE led to a significant loss of RGCs (P< 0.0001). Significantly more caspase 3+ cells were noted in these animals (P = 0.0222). They showed an increased expression of GFAP (P< 0.0002) and a higher number of microglial cells (P< 0.0001). Also more macrophages and IL-6 secretion were observed in EAE mice.ConclusionsMOG immunization leads to optic neuritis and RGC loss. EAE severity is related to the severity of optic nerve inflammation and demyelination. EAE not only affects activation of apoptotic signals, but also causes a glial response in the retina.
Highlights
Multiple sclerosis (MS) is often accompanied by optic nerve inflammation
After day 17 the clinical symptoms of EAE animals started to decline. They were significantly increased compared to Control mice (CO) animals at all points in time starting at 8 days post immunization (Figure 2)
Gliosis in experimental autoimmune encephalomyelitis retina To investigate the extent of gliosis in the retina of control and immunized mice, we examined the expression of glial fibrillary acidic protein (GFAP) in astrocytes and end-feet of Müller cells on retina crosssections
Summary
Multiple sclerosis (MS) is often accompanied by optic nerve inflammation. And some patients experience permanent vision loss. Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease with characteristic inflammatory demyelination in the central nervous system [1] Patients with this disease suffer from many disabilities like memory dysfunction, cognitive deficit and movement disorders. We immunized C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide (MOG35–55), a widely applied method to induce EAE in animals [1,5,12,13]. Both MS and EAE are characterized by inflammation and neurodegeneration in the spinal cord and the brain [12]. There are some studies describing the effect of MS and EAE in the optic nerve, the impact on the retina is still not well understood [14,15,16]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
