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Longitudinal characterization of optic nerve and retinal pathology in experimental autoimmune encephalomyelitis
Author(s): ,
P. Manogaran
Affiliations:
Department of Neurology, Neuroimmunology and Multiple Sclerosis Research, University Hospital Zurich and University of Zurich; Department of Information Technology and Electrical Engineering, Swiss Federal Institute of Technology
,
M. Samardzija
Affiliations:
Department of Ophthalmology, Lab for Retinal Cell Biology, University of Zurich
,
A.N. Schad
Affiliations:
Department of Biology, University of Zurich
,
M. Rudin
Affiliations:
Department of Information Technology and Electrical Engineering, Swiss Federal Institute of Technology; Institue for Biomedical Engineering, Swiss Federal Institute of Technology and University of Zurich; Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
,
C. Grimm
Affiliations:
Department of Ophthalmology, Lab for Retinal Cell Biology, University of Zurich
S. Schippling
Affiliations:
Department of Neurology, Neuroimmunology and Multiple Sclerosis Research, University Hospital Zurich and University of Zurich
ECTRIMS Online Library. Manogaran P. Oct 12, 2018; 228938
Praveena Manogaran
Praveena Manogaran
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Abstract: P1098

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Neurodegeneration

Background: Optic neuritis is a common manifestation in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). The visual pathway including its unmyelinated retinal axons, can serve as a prototypic model to characterize the pathological mechanisms and define the chronological sequence of events leading to neurodegeneration. Therefore, a longitudinal experiment involving optical coherence tomography (OCT) along with immunohistochemical analysis was conducted at various time points in EAE.
Methods: 20 EAE-MOG35-55 and 10 healthy female C57BL/6J mice were used in this study. Distribution of marker proteins for microglia (IBA1), gliosis (GFAP), myelin (MBP), axons (NEFM), vascular leakage (Albumin), T-cells (CD3), and retinal ganglion cells (RGC; NEUN) was assessed by immunofluorescence staining of retinal and optic nerve tissue. Retinal mRNA levels were assayed using rtPCR. Data was acquired at baseline, 7, 9, 11, 15, 20, 28 and 33 days post immunization (dpi).
Results: Activated microglia and increased GFAP signal presented as early as 7 dpi in the optic nerve and 9 dpi in the retina. At 11 dpi, massive cellular infiltration was observed including T-cells along with further increase in IBA1 and GFAP signal. Infiltration in the optic nerve reduced by 20 dpi, however microglia, GFAP, and T-cells persisted until 33 dpi. First signs of demyelination and axonal damage were observed at 11 dpi in the optic nerve, which continued until 33 dpi where profound signs of myelin disorganization and axonal degeneration were observed. In the retina, axonal degeneration was present from 20 to 33 dpi. A decrease in RGC bodies was detected at 28 and 33 dpi. Initial signs of blood-retina barrier (BRB) disruption were observed at 9 dpi followed by increased leakage into the inner retinal layers from 20 to 33 dpi.
Conclusion: BRB leakage begins early in EAE, followed by massive cellular infiltration (including peripheral T-cells) similar to previously described findings in the brain and spinal cord. The immune response within the retina appears to be secondary to optic neuritis. Demyelination and axonal degeneration occur concurrently with cellular infiltration in the optic nerve while axonal damage within the retina appears later; structural damage persisted in both compartments. These results add morphological substrate to our OCT findings reported recently. Quantitative OCT measurements and additional rtPCR analyses are currently ongoing.
Disclosure: Praveena Manogaran has received travel support from Merck Serono and Sanofi Genzyme. Sven Schippling has received research grants from Novartis and Sanofi Genzyme, and consultancy and speaking fees from Biogen, Merck Serono, Novartis, Roche, Sanofi Genzyme, and Teva. Marijana Samardzija, Anaïs Nura Schad, Christian Grimm and Markus Rudin have no conflicts of interest to disclose. This study was funded by the Swiss National Science Foundation (320030_175770).

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