Ciliary neurotrophic factor protects retinal ganglion cells from secondary cell death during acute autoimmune optic neuritis in rats.
Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS which leads to demyelination, axonal destruction and neuronal loss in the early stages. Available therapies mainly target the inflammatory component of the disease but fail to prevent neurodegeneration. To investigate the effect of ciliary neurotrophic factor (CNTF) on the survival of retinal ganglion cells (RGCs), the neurons that form the axons of the optic nerve, we used a rat model of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis. Optic neuritis in this model was diagnosed by recording visual evoked potentials, and RGC function was monitored by measuring electroretinograms. This study demonstrates that CNTF has a neuroprotective effect on affected RGCs during acute optic neuritis. Furthermore, we demonstrate that CNTF exerts its neuroprotective effect through activation of the Janus kinase/signal transducer and activator of transcription pathway, mitogen activated protein kinases and a shift in the Bcl-2 family of proteins towards the anti-apoptotic side. In summary, our results demonstrate that CNTF can serve as an effective neuroprotective treatment in a rat model of MS that especially reflects the neurodegenerative aspects of this disease.
Maier
Katharina
K
Neurologische Universitätsklinik, Göttingen, Germany. kmaier@gwdg.de
Rau
Christian R
CR
Storch
Maria K
MK
Sättler
Muriel B
MB
Demmer
Iris
I
Weissert
Robert
R
Taheri
Naimeh
N
Kuhnert
Antje V
AV
Bähr
Mathias
M
Diem
Ricarda
R
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000627:therapeutic use*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage; D005456:Fluorescent Dyes; D005786:Gene Expression Regulation / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009902:Optic Neuritis / Q000473:pathology / Q000517:prevention & control*; D010775:Photic Stimulation / Q000379:methods; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D012165:Retinal Ganglion Cells / Q000187:drug effects*; D050796:STAT3 Transcription Factor; D013266:Stilbamidines; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014793:Visual Cortex / Q000187:drug effects / Q000503:physiopathology; D051028:bcl-2-Associated X Protein
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D020934:Ciliary Neurotrophic Factor; D004268:DNA-Binding Proteins; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005456:Fluorescent Dyes; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D013266:Stilbamidines; D015534:Trans-Activators; D051028:bcl-2-Associated X Protein; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one