LINGO-1 negatively regulates TrkB phosphorylation after ocular hypertension.
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.
Fu
Qing-Ling
QL
Department of Anatomy, Li Ka Shing Faculty of Medicine, and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Hu
Bing
B
Li
Xin
X
Shao
Zhaohui
Z
Shi
Jian-Bo
JB
Wu
Wutian
W
So
Kwok-Fai
KF
Mi
Sha
S
D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000378:metabolism; D002461:Cell Line, Transformed; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D047468:Immunoprecipitation; D007429:Intraocular Pressure / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009798:Ocular Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism*; D012160:Retina / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; C525164:LINGO1 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020813:Receptor, trkB