Document Detail


Inhibitory effect of an antibody to cryptic collagen type IV epitopes on choroidal neovascularization.
MedLine Citation:
PMID:  17110907     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The wet form of age-related macular degeneration (AMD) occurs as a consequence of abnormal blood vessel growth from the choroid into the retina. Pathological angiogenesis during tumor growth and ocular disease has been associated with specific exposure of cryptic extracellular matrix epitopes. We investigated the presence of cryptic collagen IV epitopes in a murine model of choroidal neovascularization (CNV), and tested the effect on blood vessel growth of H8, a humanized antibody directed against a cryptic collagen type IV epitope. METHODS: To induce experimental CNV in adult C57BL/6 mice, Bruch's membrane was ruptured using a diode laser. Subsequently, mice were treated with daily intraperitoneal (i.p.) injections of either H8 (10 mg/kg or 30 mg/kg) or an isotype-matched antibody control. Two weeks postinjection, choroidal flat mounts were immunostained with the blood vessel marker platelet/endothelial cell adhesion molecule-1 (PECAM-1) and H8. CNV was visualized using fluorescence microscopy and the CNV lesion area measured using Open Lab software. RESULTS: Collagen type IV and the cryptic epitope were observed at the site of laser-induced lesions. Staining with H8 was first observed three days post injury, two days after MMP2 expression in CNV lesions, becoming most intense five days following laser injury and extending beyond the area of neovascularization. At 14 days post injury, H8 staining was reduced in intensity, colocalized with the area of CNV, and was nearly absent from the underlying choroidal vessels. In addition, mice treated with H8 had a significant dose-dependent decrease in the area of CNV as compared to isotype-matched antibody controls. CONCLUSIONS: Results suggest that exposure of cryptic collagen type IV epitopes is associated with the incidence of CNV and that the humanized antibody H8 may provide a new treatment for CNV.
Authors:
Nobuo Jo; Meihua Ju; Kazuaki Nishijima; Gregory S Robinson; Anthony P Adamis; David T Shima; Carolina Mailhos
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Publication Detail:
Type:  Journal Article     Date:  2006-10-26
Journal Detail:
Title:  Molecular vision     Volume:  12     ISSN:  1090-0535     ISO Abbreviation:  Mol. Vis.     Publication Date:  2006  
Date Detail:
Created Date:  2006-11-19     Completed Date:  2006-12-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9605351     Medline TA:  Mol Vis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1243-9     Citation Subset:  IM    
Affiliation:
OSI Eyetech, Eyetech Research Center, Lexington, MA 02421, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies / immunology,  pharmacology*
Choroidal Neovascularization / etiology,  immunology,  prevention & control*
Collagen Type IV / immunology*
Epitopes / immunology*,  metabolism
Extracellular Matrix / immunology
Eye / drug effects,  metabolism
Eye Injuries / immunology,  metabolism
Hot Temperature
Immunohistochemistry / methods
Lasers*
Male
Matrix Metalloproteinase 2 / pharmacology
Mice
Mice, Inbred C57BL
Protein Denaturation
Radiation Injuries / immunology,  metabolism
Staining and Labeling
Time Factors
Chemical
Reg. No./Substance:
0/Antibodies; 0/Collagen Type IV; 0/Epitopes; EC 3.4.24.24/Matrix Metalloproteinase 2

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