Purchase this article with an account.
Heiko Schmid, Lioba Horstmann, Florian Kurschus, Ari Waisman, Burkhard Dick, Stephanie Joachim; Glia alterations in the retina of a multiple sclerosis animal model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5588.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Patients suffering from Multiple Sclerosis often experience optic nerve inflammation. In some cases, these patients also are affected by permanent vision loss, but so far the mechanisms are still unclear. Earlier studies have shown a degeneration of RGCs in the retina of EAE animals. We investigated the morphological changes in the retina in a myelin oligodendrocyte protein (MOG), an experimental autoimmune encephalomyelitis (EAE) mouse model. We wanted to find out, how MOG treatment influences macroglial and microglial responses indicating inflammatory mechanisms potentially leading to loss of vision.
C57BL/6 mice (5 eyes) were immunized with 100 µg MOG35-55-peptides in complete Freund’s adjuvant containing Mycobacterium tuberculosis and Pertussis toxin. Control mice (7 eyes) received NaCl instead of MOG. Mice were examined daily using a paralysis scoring system ranging from 0 (no signs) to 5 (complete paralysis). Retina cross-sections were stained with H&E and Bielschowsky’s silver impregnation 3 weeks after immunization. Immunohistochemistry was performed in retina using antibodies against Caspase 3, GFAP, Iba1 and DAPI. Excerpts (800x610 pixel) of pictures were taken and Iba1+ and Caspase 3+ cells were counted in a masked fashion. GFAP+ labeled area and fluorescence intensity was measured using ImageJ. Data are represented as mean ± SEM. Statistical analysis was performed using Student’s T-test.
MOG35-55 treated animals experienced clinical EAE symptoms starting day 8-18 with a peak after 15 days. MOG immunized mice showed an increased expression of GFAP (area: CO: 2.08±0.08, EAE: 2.71±0.1, p= 0.000003; intensity: CO: 0.36±0.02, EAE: 0.47±0.03, p=0.002) and an increased amount of microglia and macrophages (CO: 0.77±0.06, EAE: 1.82±0.08, p<0.0001) in the GCL and IPL but had intact retinal layers with no sign of degeneration. Staining with Caspase 3 also showed significantly more Caspase 3+ cells in the retinal ganglion cell layer of MOG immunized animals (CO: 4.6±0.24, EAE: 5.5±0.36, p=0.022).
MOG immunization is known to cause optic neuritis. We could show that immunization with MOG also affects the retina by an activation of apoptotic signals and microglial and macrophage responses. However, these changes do not disrupt other retinal layers. Activation of microglia and macrophages seems to play an important role in the retina of EAE animals and the glial subtypes have to be investigated.
This PDF is available to Subscribers Only