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LINGO‐1 negatively regulates TrkB phosphorylation after ocular hypertension
Author(s) -
Fu QingLing,
Hu Bing,
Li Xin,
Shao Zhaohui,
Shi JianBo,
Wu Wutian,
So KwokFai,
Mi Sha
Publication year - 2010
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07127.x
Subject(s) - tropomyosin receptor kinase b , antagonism , neurotrophic factors , neurotrophin , retina , brain derived neurotrophic factor , antagonist , retinal ganglion cell , pharmacology , receptor , neuroscience , biology , medicine
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.