Contributions
Abstract: P1101
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurophysiology
Background: Experimental Autoimmune Encephalomyelitis (EAE) is a disease model of Multiple Sclerosis (MS) induced by injecting myelin oligodendrocyte glycoprotein (MOG). Although correlation between visual evoked potential (VEP) latencies and retinal neuroaxonal thinning measured with optical coherence tomography (OCT) is known in MS patients, the relationship between the two phenomena in preclinical models still needs further exploration. We investigated the correlation between the extent of VEPs and OCT abnormalities in MOG-EAE.
Methods: 24 Dark Agouti (DA) rats were tested: 12 immunized with MOG (EAE) and 12 healthy (H) with daily monitoring of body weight and EAE score. VEPs, OCT and histology were performed in selected animals at 21 (n=3), 34 (n=4) and 47 (n=5) days post injection (dpi). VEPs and thickness of retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCL/IPL) measured with OCT were obtained in H at all time points. VEP latencies and retinal layers >2 Z-score of H were considered abnormal. For the correlation analysis, Spearman"s correlations coefficient was used.
Results and conclusions: VEPs at 21 dpi were delayed in 4/6 EAE. At 34 dpi, 3/8 EAE eyes did not respond to visual stimuli and 2/8 eyes presented slow VEPs. At 47 dpi VEPs were absent in 5/10 EAE eyes and the remaining EAE eyes presented delayed latencies, suggesting that axonal loss and/or demyelination occurred in EAE, starting at early stages of the disease. RNFL of EAE was thinner at all time points, whereas atrophy of ganglion cell layer/inner plexiform layer (GCL/IPL) was not evident until 47 dpi. In EAE, VEP latency was negatively correlated with GCL/IPL thickness (rho=-0.633, p=0.011), whereas a trend was found with RNFL (rho=-0.449, p=0.093). At histology, EAE ONs presented severe demyelination, axonal loss and infiltrating microglia at 47 dpi, which were less evident at 21 and 34 dpi. The correlation between the severity of VEPs delays, detected even earlier than neuroaxonal loss evident at OCT, suggests that demyelination and axonal loss are associated in MOG EAE. The better correlation of GCL/IPL with respect to RNFL is consistent with the knowledge that the latter measure could be confounded by edema reported in the acute phases of optic neuritis. Moreover, these results confirm suggest the usefulness of both methods to monitor demyelination and neurodegeneration in vivo in EAE, providing quantitative measures for preclinical drug development.
Disclosure: All the authors of this poster have nothing to disclose.
Abstract: P1101
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Neurophysiology
Background: Experimental Autoimmune Encephalomyelitis (EAE) is a disease model of Multiple Sclerosis (MS) induced by injecting myelin oligodendrocyte glycoprotein (MOG). Although correlation between visual evoked potential (VEP) latencies and retinal neuroaxonal thinning measured with optical coherence tomography (OCT) is known in MS patients, the relationship between the two phenomena in preclinical models still needs further exploration. We investigated the correlation between the extent of VEPs and OCT abnormalities in MOG-EAE.
Methods: 24 Dark Agouti (DA) rats were tested: 12 immunized with MOG (EAE) and 12 healthy (H) with daily monitoring of body weight and EAE score. VEPs, OCT and histology were performed in selected animals at 21 (n=3), 34 (n=4) and 47 (n=5) days post injection (dpi). VEPs and thickness of retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCL/IPL) measured with OCT were obtained in H at all time points. VEP latencies and retinal layers >2 Z-score of H were considered abnormal. For the correlation analysis, Spearman"s correlations coefficient was used.
Results and conclusions: VEPs at 21 dpi were delayed in 4/6 EAE. At 34 dpi, 3/8 EAE eyes did not respond to visual stimuli and 2/8 eyes presented slow VEPs. At 47 dpi VEPs were absent in 5/10 EAE eyes and the remaining EAE eyes presented delayed latencies, suggesting that axonal loss and/or demyelination occurred in EAE, starting at early stages of the disease. RNFL of EAE was thinner at all time points, whereas atrophy of ganglion cell layer/inner plexiform layer (GCL/IPL) was not evident until 47 dpi. In EAE, VEP latency was negatively correlated with GCL/IPL thickness (rho=-0.633, p=0.011), whereas a trend was found with RNFL (rho=-0.449, p=0.093). At histology, EAE ONs presented severe demyelination, axonal loss and infiltrating microglia at 47 dpi, which were less evident at 21 and 34 dpi. The correlation between the severity of VEPs delays, detected even earlier than neuroaxonal loss evident at OCT, suggests that demyelination and axonal loss are associated in MOG EAE. The better correlation of GCL/IPL with respect to RNFL is consistent with the knowledge that the latter measure could be confounded by edema reported in the acute phases of optic neuritis. Moreover, these results confirm suggest the usefulness of both methods to monitor demyelination and neurodegeneration in vivo in EAE, providing quantitative measures for preclinical drug development.
Disclosure: All the authors of this poster have nothing to disclose.