Inflammatory demyelination induces glia alterations and ganglion cell loss in the retina of an experimental autoimmune encephalomyelitis model

Journal of Neuroinflammation

Stephanie C Joachim¹  HBurkhard Dick¹  Florian C Kurschus²  André P Heinen²  Heiko Schmid¹  Lioba Horstmann¹ 

[1] Experimental Eye Research Institute, Ruhr University Eye Hospital, In der Schornau 23-25, 44892 Bochum, Germany;Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University, Obere Zahlbacherstrasse. 67, 55131 Mainz, Germany

关键词: Apoptosis;    RGC;    Retina;    Optic nerve;    Demyelination;    Glia;    Optic neuritis;    Multiple sclerosis;    MOG;    EAE;   

Others  :  1151878
DOI  :  10.1186/1742-2094-10-120

 received in 2013-04-26, accepted in 2013-09-24,  发布年份 2013

【 摘 要 】

Background

Multiple sclerosis (MS) is often accompanied by optic nerve inflammation. And some patients experience permanent vision loss. We examined if the grade of optic nerve infiltration and demyelination affects the severity of clinical signs in an experimental autoimmune encephalomyelitis (EAE) model. The loss of retinal ganglion cells (RGC) and alterations in glia activity were also investigated.

Methods

C57BL/6 mice were immunized with peptide MOG_35-55 in complete Freund’s adjuvant (CFA) and controls received PBS in CFA. Then 23 days post immunization eyes were prepared for flatmounts and stained with Nissl to evaluated neuronal density. Clinical EAE symptoms as well as cell infiltration and demyelination in the optic nerve were examined. Retinal sections were stained with hematoxylin and eosin and silver stain. Immunohistochemistry was used to label RGCs (Brn-3a), apoptotic cells (caspase 3), macroglia (glial fibrillary acidic protein (GFAP)), microglia (Iba1), macrophages (F 4/80) and interleukin-6 (IL-6) secretion.

Results

EAE symptoms started at day 8 and peaked at day 15. Cell infiltrations (P = 0.0047) and demyelination (P = 0.0018) of EAE nerves correlated with the clinical score (r > 0.8). EAE led to a significant loss of RGCs (P< 0.0001). Significantly more caspase 3⁺ cells were noted in these animals (P = 0.0222). They showed an increased expression of GFAP (P< 0.0002) and a higher number of microglial cells (P< 0.0001). Also more macrophages and IL-6 secretion were observed in EAE mice.

Conclusions

MOG immunization leads to optic neuritis and RGC loss. EAE severity is related to the severity of optic nerve inflammation and demyelination. EAE not only affects activation of apoptotic signals, but also causes a glial response in the retina.

【 授权许可】

   
2013 Horstmann et al.; licensee BioMed Central Ltd.

【 图 表 】

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