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Lioba Horstmann, Heiko Schmid, Florian Kurschus, Ari Waisman, Burkhard Dick, Stephanie Joachim; Retinal ganglion cell loss and inflammatory demyelination in an experimental autoimmune encephalomyelitis model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1417.
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© ARVO (1962-2015); The Authors (2016-present)
Multiple sclerosis is a neurodegenerative disease that is often accompanied by optic nerve inflammation and demyelination. We examined in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, if the neurodegenerative disorder of the animals is correlated with the retinal ganglion cell (RGC) death or optic nerve inflammation and demyelination.
C57BL/6 mice (N=8) were immunized with 100 µg MOG35-55 peptide in complete Freund’s adjuvant containing Mycobacterium tuberculosis and Pertussis toxin. Control mice (N=9) were treated the same except MOG was replaced by NaCl. Mice were clinicaly examined with an EAE scoring system from 0 (no) to 5 (complete paralysis). 23 days post-immunization, eyes were prepared for flatmounts and stained with Nissl to count the RGCs. Longitudinal optic nerve (ON) sections were stained with hematoxylin/eosin (H&E) to evaluate the inflammatory cell infiltration using a scale ranging from 0 (no) to 4 (massive infiltration). Luxol fast blue (LFB) staining was also performed to analyze demyelination using a score from 0 (no) to 2 (strong demyelination). Student’s t-test was used for statistical analysis.
MOG35-55 immunization leads to EAE symptoms starting at day 8 and peaking at day 15 (CO: 0, EAE: 2.6±0.7; p<0.0000004) post immunization. Induction of EAE caused a significant reduction of RGCs in EAE mice (312.1±8) compared to CO (359.3±7.3; p=0.00002). H&E staining showed a significant amount of cell-infiltration in areas of the ON of EAE-mice (p=0.004). The grade of infiltration correlated with the clinical EAE-score (r=0.98). LFB-staining revealed a significant loss of myelin in immunized mice (p=0.009) and also showed a correlation to the EAE-score (r=0.83). The control nerves had an intact lamellar structure and showed no or little signs of demyelination.
MOG immunization leads to clinical neurological disorders and an optic neuritis with RGC loss. Inflammation of the ON plays a role in the disease shown by the correlation of the severity of inflammation and demyelination with the clinical score.
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