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Article: Combined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma

TitleCombined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma
Authors
Keywordsneural cells
neuronal survival
neurotrophic factors
ocular hypertension
TrkB
Issue Date2009
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscience
Citation
Neuroscience, 2009, v. 162 n. 2, p. 375-382 How to Cite?
Abstract
Glaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. There are no effective neuroprotectants to treat this disorder. Brain-derived neurotrophic factor (BDNF) is well known to transiently delay RGC death in ocular hypertensive eyes. The CNS-specific leucine-rich repeat protein LINGO-1 contributes to the negative regulation to some trophic pathways. We thereby examined whether BDNF combined with LINGO-1 antagonists can promote long-term RGC survival after ocular hypertension. In this study, intraocular pressure was elevated in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. BDNF alone shows slight neuroprotection to RGCs after a long-term progress of 4 weeks following the induction of ocular hypertension. However, combination of BDNF and LINGO-1-Fc prevents RGC death in the same condition. We further identified that (1) LINGO-1 was co-expressed with BDNF receptor, TrkB in the RGCs, and (2) BDNF combined with LINGO-1-Fc activated more TrkB in the injured retina compared to BDNF alone. These results indicate that the combination of BDNF with LINGO-1 antagonist can provide long-term protection for RGCs in a chronic ocular hypertension model. TrkB may be the predominant mediator of this neuroprotection. © 2009 IBRO.
Persistent Identifierhttp://hdl.handle.net/10722/58217
ISSN
2013 Impact Factor: 3.327
2013 SCImago Journal Rankings: 1.876
ISI Accession Number ID
Funding AgencyGrant Number
NSFC30801272
RFDP200805581160
Natural Science Foundation of Guangdong Province of China8451008901000852
Science and Technology Foundation of Guangdong Province of China2006B36004010
Funding Information:

This study was supported by funding from the Jessie Ho Professorship in Neuroscience (The University of Hong Kong Foundation for Educational Development and Research Limited, and donation from Mr. George Ho), and donations from Madame Tung Shai Yun, and Madame Annie Tsao Wen Wei. This research was also supported by grants from the NSFC (30801272), RFDP (200805581160), Natural Science Foundation of Guangdong Province of China (8451008901000852) and Science and Technology Foundation of Guangdong Province of China (2006B36004010).

References

 

Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. Biogen IDEC
  4. Sun Yat-Sen University
DC FieldValueLanguage
dc.contributor.authorFu, QLen_HK
dc.contributor.authorLi, Xen_HK
dc.contributor.authorYip, HKen_HK
dc.contributor.authorShao, Zen_HK
dc.contributor.authorWu, Wen_HK
dc.contributor.authorMi, Sen_HK
dc.contributor.authorSo, KFen_HK
dc.date.accessioned2010-05-31T03:26:01Z-
dc.date.available2010-05-31T03:26:01Z-
dc.date.issued2009en_HK
dc.identifier.citationNeuroscience, 2009, v. 162 n. 2, p. 375-382en_HK
dc.identifier.issn0306-4522en_HK
dc.identifier.urihttp://hdl.handle.net/10722/58217-
dc.description.abstractGlaucoma is a progressive neuropathy characterized by loss of vision as a result of retinal ganglion cell (RGC) death. There are no effective neuroprotectants to treat this disorder. Brain-derived neurotrophic factor (BDNF) is well known to transiently delay RGC death in ocular hypertensive eyes. The CNS-specific leucine-rich repeat protein LINGO-1 contributes to the negative regulation to some trophic pathways. We thereby examined whether BDNF combined with LINGO-1 antagonists can promote long-term RGC survival after ocular hypertension. In this study, intraocular pressure was elevated in adult rats using an argon laser to photocoagulate the episcleral and limbal veins. BDNF alone shows slight neuroprotection to RGCs after a long-term progress of 4 weeks following the induction of ocular hypertension. However, combination of BDNF and LINGO-1-Fc prevents RGC death in the same condition. We further identified that (1) LINGO-1 was co-expressed with BDNF receptor, TrkB in the RGCs, and (2) BDNF combined with LINGO-1-Fc activated more TrkB in the injured retina compared to BDNF alone. These results indicate that the combination of BDNF with LINGO-1 antagonist can provide long-term protection for RGCs in a chronic ocular hypertension model. TrkB may be the predominant mediator of this neuroprotection. © 2009 IBRO.en_HK
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscienceen_HK
dc.relation.ispartofNeuroscienceen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectneural cellsen_HK
dc.subjectneuronal survivalen_HK
dc.subjectneurotrophic factorsen_HK
dc.subjectocular hypertensionen_HK
dc.subjectTrkBen_HK
dc.subject.meshBrain-Derived Neurotrophic Factor - pharmacology - therapeutic use-
dc.subject.meshGlaucoma - drug therapy - pathology - physiopathology-
dc.subject.meshMembrane Proteins - biosynthesis - genetics-
dc.subject.meshNerve Tissue Proteins - biosynthesis - genetics-
dc.subject.meshNeuroprotective Agents - pharmacology - therapeutic use-
dc.titleCombined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0306-4522&volume=162&issue=2&spage=375&epage=82&date=2009&atitle=Combined+effect+of+brain-derived+neurotrophic+factor+and+LINGO-1+fusion+protein+on+long-term+survival+of+retinal+ganglion+cells+in+chronic+glaucomaen_HK
dc.identifier.emailYip, HK:hkfyip@hku.hken_HK
dc.identifier.emailWu, W:wtwu@hkucc.hku.hken_HK
dc.identifier.emailSo, KF:hrmaskf@hkucc.hku.hken_HK
dc.identifier.authorityYip, HK=rp00285en_HK
dc.identifier.authorityWu, W=rp00419en_HK
dc.identifier.authoritySo, KF=rp00329en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.neuroscience.2009.04.075en_HK
dc.identifier.pmid19422885en_HK
dc.identifier.scopuseid_2-s2.0-67649476103en_HK
dc.identifier.hkuros173300en_HK
dc.identifier.hkuros161256-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-67649476103&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume162en_HK
dc.identifier.issue2en_HK
dc.identifier.spage375en_HK
dc.identifier.epage382en_HK
dc.identifier.isiWOS:000267787500015-
dc.publisher.placeNetherlandsen_HK
dc.identifier.scopusauthoridFu, QL=23388762000en_HK
dc.identifier.scopusauthoridLi, X=26025231300en_HK
dc.identifier.scopusauthoridYip, HK=7101980864en_HK
dc.identifier.scopusauthoridShao, Z=7202244441en_HK
dc.identifier.scopusauthoridWu, W=7407081122en_HK
dc.identifier.scopusauthoridMi, S=7004825561en_HK
dc.identifier.scopusauthoridSo, KF=34668391300en_HK

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