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Article: Blocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection

TitleBlocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transection
Authors
Issue Date2008
PublisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.org
Citation
Investigative Ophthalmology And Visual Science, 2008, v. 49 n. 3, p. 975-985 How to Cite?
Abstract
PURPOSE. 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.
Persistent Identifierhttp://hdl.handle.net/10722/67358
ISSN
2013 Impact Factor: 3.661
2013 SCImago Journal Rankings: 2.185
ISI Accession Number ID
References

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Biogen IDEC
DC FieldValueLanguage
dc.contributor.authorFu, QLen_HK
dc.contributor.authorHu, Ben_HK
dc.contributor.authorWu, Ten_HK
dc.contributor.authorPepinsky, RBen_HK
dc.contributor.authorMi, Sen_HK
dc.contributor.authorSo, KFen_HK
dc.date.accessioned2010-09-06T05:54:25Z-
dc.date.available2010-09-06T05:54:25Z-
dc.date.issued2008en_HK
dc.identifier.citationInvestigative Ophthalmology And Visual Science, 2008, v. 49 n. 3, p. 975-985en_HK
dc.identifier.issn0146-0404en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67358-
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.en_HK
dc.languageengen_HK
dc.publisherAssociation for Research in Vision and Ophthalmology. The Journal's web site is located at http://www.iovs.orgen_HK
dc.relation.ispartofInvestigative Ophthalmology and Visual Scienceen_HK
dc.titleBlocking LINGO-1 function promotes retinal ganglion cell survival following ocular hypertension and optic nerve transectionen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0146-0404&volume=49&issue=3&spage=975&epage=985&date=2008&atitle=Blocking+LINGO-1+function+promotes+retinal+ganglion+cell+survival+following+ocular+hypertension+and+optic+nerve+transectionen_HK
dc.identifier.emailSo, KF:hrmaskf@hkucc.hku.hken_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1167/iovs.07-1199en_HK
dc.identifier.pmid18326721-
dc.identifier.scopuseid_2-s2.0-41949111140en_HK
dc.identifier.hkuros151698en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-41949111140&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume49en_HK
dc.identifier.issue3en_HK
dc.identifier.spage975en_HK
dc.identifier.epage985en_HK
dc.identifier.isiWOS:000253812900023-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridFu, QL=23388762000en_HK
dc.identifier.scopusauthoridHu, B=35733928400en_HK
dc.identifier.scopusauthoridWu, T=9237315300en_HK
dc.identifier.scopusauthoridPepinsky, RB=35248984500en_HK
dc.identifier.scopusauthoridMi, S=7004825561en_HK
dc.identifier.scopusauthoridSo, KF=34668391300en_HK

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