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Article: Blocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection
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TitleBlocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection
 
AuthorsFu, QL1 2
Hu, B1 2
Wu, T1 2
Pepinsky, RB3
Mi, S3
So, KF1 2
 
Issue Date2008
 
PublisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org
 
CitationInvestigative Ophthalmology And Visual Science, 2008, v. 49 n. 3, p. 975-985 [How to Cite?]
DOI: http://dx.doi.org/10.1167/iovs.07-1199
 
AbstractPURPOSE. LINGO-1 is a functional member of the Nogo66 receptor (NgR1)/p75 and NgR1/TROY signaling complexes that prevent axonal regeneration through RhoA in the central nervous system. LINGO-1 also promotes cell death after neuronal injury and spinal cord injury. The authors sought to examine whether blocking LINGO-1 function with LINGO-1 antagonists promotes retinal ganglion cell (RGC) survival after ocular hypertension and optic nerve transection. METHODS. An experimental ocular hypertension model was induced in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. LINGO-1 expression in the retinas was investigated using immunohistochemistry and Western blotting. Soluble LINGO-1 protein (LINGO-1-Fc) and antiLINGO-1 mAb 1A7 were injected into the vitreous body to examine their effects on RGC survival after ocular hypertension and optic nerve transection. Signal transduction pathways mediating neuroprotective LINGO-1-Fc effects were characterized using Western blotting and specific kinase inhibitors. RESULTS. LINGO-1 was expressed in RGCs and up-regulated after intraocular pressure elevation. Blocking LINGO-1 function with LINGO-1 antagonists, LINGO-1-Fc and 1A7 significantly reduced RGC loss 2 and 4 weeks after ocular hypertension and also promoted RGC survival after optic nerve transection. LINGO-1-Fc treatment blocked the RhoA, JNK pathway and promoted Akt activation. LINGO-1-Fc induced Akt phosphorylation, and the survival effect of LINGO-1 antagonists was abolished by Akt phosphorylation inhibitor. CONCLUSIONS. The authors demonstrated that blocking LINGO-1 function with LINGO-1 antagonists rescues RGCs from cell death after ocular hypertension and optic nerve transection. They also delineated the RhoA and PI-3K/Akt pathways as the predominant mediator of LINGO-1-Fc neuroprotection in this paradigm of RGC death. Copyright © Association for Research in Vision and Ophthalmology.
 
ISSN0146-0404
2013 Impact Factor: 3.661
2013 SCImago Journal Rankings: 2.185
 
DOIhttp://dx.doi.org/10.1167/iovs.07-1199
 
ISI Accession Number IDWOS:000253812900023
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorFu, QL
 
dc.contributor.authorHu, B
 
dc.contributor.authorWu, T
 
dc.contributor.authorPepinsky, RB
 
dc.contributor.authorMi, S
 
dc.contributor.authorSo, KF
 
dc.date.accessioned2010-09-06T05:54:25Z
 
dc.date.available2010-09-06T05:54:25Z
 
dc.date.issued2008
 
dc.description.abstractPURPOSE. LINGO-1 is a functional member of the Nogo66 receptor (NgR1)/p75 and NgR1/TROY signaling complexes that prevent axonal regeneration through RhoA in the central nervous system. LINGO-1 also promotes cell death after neuronal injury and spinal cord injury. The authors sought to examine whether blocking LINGO-1 function with LINGO-1 antagonists promotes retinal ganglion cell (RGC) survival after ocular hypertension and optic nerve transection. METHODS. An experimental ocular hypertension model was induced in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. LINGO-1 expression in the retinas was investigated using immunohistochemistry and Western blotting. Soluble LINGO-1 protein (LINGO-1-Fc) and antiLINGO-1 mAb 1A7 were injected into the vitreous body to examine their effects on RGC survival after ocular hypertension and optic nerve transection. Signal transduction pathways mediating neuroprotective LINGO-1-Fc effects were characterized using Western blotting and specific kinase inhibitors. RESULTS. LINGO-1 was expressed in RGCs and up-regulated after intraocular pressure elevation. Blocking LINGO-1 function with LINGO-1 antagonists, LINGO-1-Fc and 1A7 significantly reduced RGC loss 2 and 4 weeks after ocular hypertension and also promoted RGC survival after optic nerve transection. LINGO-1-Fc treatment blocked the RhoA, JNK pathway and promoted Akt activation. LINGO-1-Fc induced Akt phosphorylation, and the survival effect of LINGO-1 antagonists was abolished by Akt phosphorylation inhibitor. CONCLUSIONS. The authors demonstrated that blocking LINGO-1 function with LINGO-1 antagonists rescues RGCs from cell death after ocular hypertension and optic nerve transection. They also delineated the RhoA and PI-3K/Akt pathways as the predominant mediator of LINGO-1-Fc neuroprotection in this paradigm of RGC death. Copyright © Association for Research in Vision and Ophthalmology.
 
dc.description.naturelink_to_OA_fulltext
 
dc.identifier.citationInvestigative Ophthalmology And Visual Science, 2008, v. 49 n. 3, p. 975-985 [How to Cite?]
DOI: http://dx.doi.org/10.1167/iovs.07-1199
 
dc.identifier.doihttp://dx.doi.org/10.1167/iovs.07-1199
 
dc.identifier.epage985
 
dc.identifier.hkuros151698
 
dc.identifier.isiWOS:000253812900023
 
dc.identifier.issn0146-0404
2013 Impact Factor: 3.661
2013 SCImago Journal Rankings: 2.185
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid18326721
 
dc.identifier.scopuseid_2-s2.0-41949111140
 
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dc.identifier.urihttp://hdl.handle.net/10722/67358
 
dc.identifier.volume49
 
dc.languageeng
 
dc.publisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofInvestigative Ophthalmology and Visual Science
 
dc.relation.referencesReferences in Scopus
 
dc.titleBlocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Biogen IDEC