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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
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TitleCombined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma
 
AuthorsFu, QL4 1
Li, X4
Yip, HK1 2 2
Shao, Z3
Wu, W4 1
Mi, S3
So, KF1 2 2
 
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
 
CitationNeuroscience, 2009, v. 162 n. 2, p. 375-382 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuroscience.2009.04.075
 
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.
 
ISSN0306-4522
2012 Impact Factor: 3.122
2012 SCImago Journal Rankings: 1.498
 
DOIhttp://dx.doi.org/10.1016/j.neuroscience.2009.04.075
 
ISI Accession Number IDWOS:000267787500015
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).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorFu, QL
 
dc.contributor.authorLi, X
 
dc.contributor.authorYip, HK
 
dc.contributor.authorShao, Z
 
dc.contributor.authorWu, W
 
dc.contributor.authorMi, S
 
dc.contributor.authorSo, KF
 
dc.date.accessioned2010-05-31T03:26:01Z
 
dc.date.available2010-05-31T03:26:01Z
 
dc.date.issued2009
 
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.
 
dc.description.naturepostprint
 
dc.identifier.citationNeuroscience, 2009, v. 162 n. 2, p. 375-382 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuroscience.2009.04.075
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuroscience.2009.04.075
 
dc.identifier.epage382
 
dc.identifier.hkuros173300
 
dc.identifier.hkuros161256
 
dc.identifier.isiWOS:000267787500015
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).

 
dc.identifier.issn0306-4522
2012 Impact Factor: 3.122
2012 SCImago Journal Rankings: 1.498
 
dc.identifier.issue2
 
dc.identifier.openurl
 
dc.identifier.pmid19422885
 
dc.identifier.scopuseid_2-s2.0-67649476103
 
dc.identifier.spage375
 
dc.identifier.urihttp://hdl.handle.net/10722/58217
 
dc.identifier.volume162
 
dc.languageeng
 
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/neuroscience
 
dc.publisher.placeNetherlands
 
dc.relation.ispartofNeuroscience
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
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.subjectneural cells
 
dc.subjectneuronal survival
 
dc.subjectneurotrophic factors
 
dc.subjectocular hypertension
 
dc.subjectTrkB
 
dc.titleCombined effect of brain-derived neurotrophic factor and LINGO-1 fusion protein on long-term survival of retinal ganglion cells in chronic glaucoma
 
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
  4. Sun Yat-Sen University