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Research on Mechanisms of Visual Damage in a Mice Model of Experimental Autoimmune Encephalomyelitis

Author: ZhangYue
Tutor: GuanYangTai
School: Second Military Medical University
Course: Neurology
Keywords: experimental autoimmune encephalomyelitis multiple sclerosis optic neuritis retinal ganglion cell amacrine cell
CLC: R-332
Type: Master's thesis
Year: 2013
Downloads: 8
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Abstract


Objective: To investigate mechanisms underlying visual dysfunction in a micedisease model of experimental autoimmune encephalomyelitis(EAE) by monitoringchanges in dopaminergic amacrine cell(DAC) numbers, eye-specific segregation andretinofugal projection.Methods: Female C57BL/6mice were injected subcutaneously with MOG35-55emulsified with complete Freund’s adjuvant(CFA) to induce EAE in experimentalgroup(n=50). Control mice were sham immunized with an equal volume of saline(n=20).Clinically progression of EAE was scored daily according to Webster criteria. Dye eyeinjection within vitreous were performed binocularly at different time points.48hrs afterwhole eye injection, mice were sacrificed and transcardially perfused. Presence ofinflammatory cells infiltration in optic nerves was observed by hematoxylin and eosinstaining and Luxol Fast Blue. To assess integrity of retinofugal pathway, whole-mountbrains were viewed by fluorescent microscopy. For eye segregation experiments, brainsslices were sectioned coronally or sagittally using a vibratome. Slices of lateral geniculatenucleus(LGN) and superior colliculus(SC) with the largest projection area were collectedand analysis. Detected the changes of DACs numbers by immunofluorscence staining,quantifying tyrosine hydroxylase-positive cell bodies.Results:1. Chronic progressive of EAE induced by MOG35-55.Clinical EAE was first detected at day12after immunization, with the incidence of96%. The severity score was3.53±0.75when EAE course reaching a chronic level. Theincidence of optic neuritis was77.1%.2. Eye-specific segregation defects in the LGN and SC of EAE.Eye-specific segregation in the LGN and superior colliculus was disrupted by day20post-immunization. EAE increased the fraction of the LGN covered by ipsilateral RGCafferents and seemed to cause a similar increase in the overlap between ipsilateral andcontralateral projections by day20post-immunization, and increased through the next days.Eye-specific segregation defects was also first detected in the superior colliculus at day20after immunization. At day25post-immunization, the overlap increased to the peak incomparison to that in control mice and the difference reached statisticalsignificance(P=0.0012). 3. Significant DACs loss in eyes from EAE.No difference in DACs numbers was found between control mice eyes and EAEeyes15days post-immunization. Fewer DACs were first detected at day20afterimmunization in the retinas of EAE mice, with continued decline in DACs numbers. By25days post-immunization, significant fewer DACs were observed in comparison withcontrol mice(P<0.001).4. Whole-mount brain from EAE mice demonstrated normal state of visual pathwaymorphologically at the15thday, the20thday, the25thday and the30thday afterimmunization. Maintenance of visual pathway was also observed in control mice atdifferent time points. Outline of the LGN was obscure while the SC still intact in EAEmice40days post-immunization, suggesting that previous retinofugal pathway wassignificantly damaged with high incidence of83.33%.Conclusion:1. C57BL/6mice immunized with MOG35-55successfully exhibit achronic persistent EAE course. MOG-induced EAE proved to be an ideal animal model tostudy ON and MS for its stability and obvious pathological changes in optic nerves.2. Visual dysfunction occurring in EAE mainly correlates with failure of signalprocessing and transmitting.3. Visual information processing disorders may triggered by abnormal cell-coupling,resulting from loss of retinal dopaminergic amacrine cells in EAE.4. Previous retinofugal pathway was significantly damaged from central-side to retina,thus leading to signal transmitting blockage.

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