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rdf:type |
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lifeskim:mentions |
umls-concept:C0009498,
umls-concept:C0026336,
umls-concept:C0026339,
umls-concept:C0175677,
umls-concept:C0242383,
umls-concept:C0302600,
umls-concept:C0392756,
umls-concept:C0599894,
umls-concept:C1419621,
umls-concept:C1521840,
umls-concept:C1523987,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1999216
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pubmed:dateCreated |
2010-8-16
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pubmed:abstractText |
Genetic variations in complement factor H (fH), an inhibitor of the complement alternative pathway (CAP), and oxidative stress are associated with age-related macular degeneration (AMD). Recently, novel complement therapeutics have been created with the capacity to be "targeted" to sites of complement activation. One example is our recombinant form of fH, CR2-fH, which consists of the N-terminus of mouse fH that contains the CAP-inhibitory domain, linked to a complement receptor 2 (CR2) targeting fragment that binds complement activation products. CR2-fH was investigated in vivo in the mouse model of choroidal neovascularization (CNV) and in vitro in oxidatively stressed RPE cell monolayers. RPE deterioration and CNV development were found to require CAP activation, and specific CAP inhibition by CR2-fH reduced the loss of RPE integrity and angiogenesis in CNV. In both the in vivo and in vitro paradigm of RPE damage, a model requiring molecular events known to be involved in AMD, complement-dependent VEGF production, was confirmed. These data may open new avenues for AMD treatment strategies.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
0065-2598
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pubmed:author |
pubmed-author:CoughlinBethB,
pubmed-author:FerreiraViviana PVP,
pubmed-author:GilkesonGary SGS,
pubmed-author:HolersV MichaelVM,
pubmed-author:HuangYuxiangY,
pubmed-author:KunchithapauthamKannanK,
pubmed-author:LongQinQ,
pubmed-author:PangburnMichael KMK,
pubmed-author:RennerBrandonB,
pubmed-author:RohrerBärbelB,
pubmed-author:ThurmanJoshua MJM,
pubmed-author:TomlinsonStephenS
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pubmed:issnType |
Print
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pubmed:volume |
703
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
137-49
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pubmed:meshHeading |
pubmed-meshheading:20711712-Animals,
pubmed-meshheading:20711712-Cell Line,
pubmed-meshheading:20711712-Choroidal Neovascularization,
pubmed-meshheading:20711712-Complement Inactivating Agents,
pubmed-meshheading:20711712-Complement Pathway, Alternative,
pubmed-meshheading:20711712-Disease Models, Animal,
pubmed-meshheading:20711712-Humans,
pubmed-meshheading:20711712-Macular Degeneration,
pubmed-meshheading:20711712-Mice,
pubmed-meshheading:20711712-Models, Biological,
pubmed-meshheading:20711712-Oxidative Stress,
pubmed-meshheading:20711712-Retinal Pigment Epithelium,
pubmed-meshheading:20711712-Vascular Endothelial Growth Factor A
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pubmed:year |
2010
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pubmed:articleTitle |
A targeted inhibitor of the complement alternative pathway reduces RPE injury and angiogenesis in models of age-related macular degeneration.
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pubmed:affiliation |
Department of Ophthalmology, Medical University of South Carolina, Charleston, SC, USA. rohrer@musc.edu
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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