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Abstract #25781 Published in IGR 12-2

LINGO-1 negatively regulates TrkB phosphorylation after ocular hypertension

Fu Q-L; Hu B; Li X; Shao Z; Shi J-B; Wu W; So K-F; Mi S
European Journal of Neuroscience 2010; 31: 1091-1097

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The antagonism of LINGO-1, a CNS-specific negative regulator of neuronal survival, was shown to promote short-term survival of retinal ganglion cell (RGC) in an ocular hypertension model. LINGO-1 antagonists, combined with brain-derived neurotrophic factor (BDNF), can increase the length of neuron survival through an unclear molecular mechanism. To determine the relationship between LINGO-1 and BDNF/TrkB receptor in neuronal protection, we show here that LINGO-1 forms a receptor complex with TrkB and negatively regulates its activation in the retina after ocular hypertension injury. LINGO-1 antagonist antibody 1A7 or soluble LINGO-1 (LINGO-1-Fc) treatment upregulates phospho-TrkB phosphorylation and leads to RGC survival after high intraocular pressure injury. This neuronal protective effect was blocked by anti-BDNF antibody. LINGO-1 antagonism therefore promotes RGC survival by regulating the BDNF and TrkB signaling pathway after ocular hypertension.

S. Mi. Discovery Neurobiology Department, Biogen Idec, 14 Cambridge Center, Cambridge, MA, United States. sha.mi@biogenidec.com

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Classification:

3.6 Cellular biology (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)

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