title: LINGO-1 negatively regulates TrkB phosphorylation after ocular hypertension.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qing-Ling
authors.initials: QL
authors.lastname: Fu
authors.forename: Bing
authors.initials: B
authors.lastname: Hu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Shao
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Shi
authors.forename: Wutian
authors.initials: W
authors.lastname: Wu
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: Sha
authors.initials: S
authors.lastname: Mi
mesh_terms: 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
chemical_list: D000906:Antibodies; D019208:Brain-Derived Neurotrophic Factor; C525164:LINGO1 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020813:Receptor, trkB