Purchase this article with an account.
Lioba Horstmann, Xiomara Pedreiturria, Sandra Kuehn, Lars Kühl, Kathrin Haak, Heiko Schmid, Ingo Kleiter, Stephanie C Joachim; Activation of glial cells in retina and optic nerve of an experimental autoimmune encephalomyelitis model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4947.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The experimental autoimmune encephalomyelitis (EAE) is a common model for Multiple Sclerosis. It is known that optic nerve degeneration occurs in EAE. We investigated a late time point in this model to gain better understanding for the pathological pathway, especially in regard to glia cells.
B6 mice were immunized with MOG35-55-peptide in CFA plus PTx. Control groups received CFA/PTx or PBS only (n=3-7/group). 60 days post immunization immunohistochemistry of the retina was performed to specifically label RGCs (Brn-3a), macroglia (GFAP), Müller cells (vimentin), microglia (Iba1), and bipolar cells (PKCα). Optic nerves (ON) were also stained with GFAP and Iba1. Additionally, ON sections were stained with HE, to evaluate the inflammatory cell infiltration, and LFB, to determine the grade of demyelination. Cell counts and area analysis was conducted with ImageJ. A scoring system was used to evaluate the HE and LFB stained sections. Statistical analysis was performed using Student’s t-test.
EAE symptoms started at day 6 and peaked at day 12. The clinical EAE score correlated with the cell infiltration and demyelination in the ON. We noted a significantly higher number of microglia cells in the optic nerve of MOG-EAE animals (11.4±0.8) compared to the PBS (5.3±0.6, p<0.0001) and CFA/PTx control group (6.6±0.7, p<0.0001). Macroglia area was comparable in all groups, but MOG nerves exhibited severe damage. A significant RGC loss was seen in MOG retinas (33.3±3.2) in contrast to the CFA/PTx (59.4±5.4, p<0.0001) and the PBS control group (56.0±6.1, p<0.0001). MOG animals showed an increased expression of retinal GFAP (2.3±0.2%) in comparison to CFA/PTx (1.5±0.2%, p<0.0001) and PBS animals (1.2±0.2%, p<0.0001) and no alterations in the vimentin area (p>0.05).
In accordance with findings from acute EAE, MOG immunization also led to optic neuritis during chronic EAE. The strong microglia migration into the optic nerve was associated with axonal damage, likely due to the release of toxic compounds. The distinct activation of macroglia in the retina could be a result of the observed RGC loss. Whether this glia activation is an attempted repair mechanism or adversely affects RGCs is still unclear.
This PDF is available to Subscribers Only