Document Detail


Pathogenic role of the Wnt signaling pathway activation in laser-induced choroidal neovascularization.
MedLine Citation:
PMID:  23211829     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Choroidal neovascularization (CNV) is a severe complication of AMD. The Wnt signaling pathway has been shown to mediate angiogenesis. The purpose of this study was to investigate the pathogenic role of the Wnt pathway in CNV and explore the therapeutic potential of a novel Wnt signaling inhibitor in CNV.
METHODS: Adult rats and mice were photocoagulated using diode laser to induce CNV. On the same day, the animals were intravitreally injected with a monoclonal antibody (Mab2F1) blocking LRP6 or nonspecific mouse IgG. The Wnt signaling activation and target gene expression in the eyecup were determined by Western blot analysis. Fundus angiography was used to examine leakage from the laser lesion. CNV areas were measured on choroidal flatmount using FITC-dextran.
RESULTS: Levels of Wnt pathway components and Wnt target gene expression were elevated in both laser-induced CNV rat and mouse eyecups, suggesting activation of the Wnt pathway. Significant suppression of Wnt signaling was observed in the Mab2F1 treatment group. Mab2F1 decreased vascular leakage from CNV lesions and reduced the neovascular area in laser-induced CNV rats. Mab2F1 inhibited the hypoxia-induced activation of Wnt signaling in cultured RPE cells. Mab2F1 also ameliorated retinal inflammation and vascular leakage in the eyecups of very low-density lipoprotein receptor knockout mice, a model of subretinal neovascularization.
CONCLUSIONS: The Wnt pathway is activated in the laser-induced CNV models and plays a pathogenic role in CNV. Blockade of Wnt signaling using an anti-LRP6 antibody has therapeutic potential in CNV.
Authors:
Yang Hu; Ying Chen; Mingkai Lin; Kyungwon Lee; Robert A Mott; Jian-xing Ma
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-07
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  54     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-08     Completed Date:  2013-03-05     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  141-54     Citation Subset:  IM    
Affiliation:
Department of Physiology, University of Oklahoma, Health Sciences Center, Oklahoma City, Oklahoma, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Anoxia / metabolism,  pathology
Antibodies, Monoclonal / pharmacology
Cell Line
Choroidal Neovascularization* / etiology,  metabolism,  pathology
Disease Models, Animal
Humans
Lasers / adverse effects
Ligands
Low Density Lipoprotein Receptor-Related Protein-6 / antagonists & inhibitors,  immunology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Rats
Rats, Inbred BN
Receptors, LDL / genetics
Retinal Pigment Epithelium / cytology
Wet Macular Degeneration* / etiology,  metabolism,  pathology
Wnt Signaling Pathway / physiology*
Grant Support
ID/Acronym/Agency:
EY012231/EY/NEI NIH HHS; EY018659/EY/NEI NIH HHS; EY019309/EY/NEI NIH HHS; P20RR024215/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Ligands; 0/Low Density Lipoprotein Receptor-Related Protein-6; 0/Lrp6 protein, mouse; 0/Receptors, LDL; 0/VLDL receptor
Comments/Corrections

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