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Molecular Pharmacology

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Research ArticleArticle

Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an α5β1 Integrin Antagonist

Naoyasu Umeda, Shu Kachi, Hideo Akiyama, Grit Zahn, Doerte Vossmeyer, Roland Stragies and Peter A. Campochiaro
Molecular Pharmacology June 2006, 69 (6) 1820-1828; DOI: https://doi.org/10.1124/mol.105.020941
Naoyasu Umeda
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Shu Kachi
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Hideo Akiyama
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Grit Zahn
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Doerte Vossmeyer
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Roland Stragies
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Peter A. Campochiaro
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Abstract

Integrin α5β1 plays an important role in developmental angiogenesis, but its role in various types of pathologic neovascularization has not been completely defined. In this study, we found strong up-regulation of α5β1 in choroidal neovascularization. Implantation of an osmotic pump delivering 1.5 or 10 μg/h (∼1.8 or 12 mg/kg/day) of 3-(2-{1-alkyl-5-[(pyridin-2-ylamino)-methyl]-pyrrolidin-3-yloxy}-acetylamino)-2-(alkylamino)-propionic acid (JSM6427), a selective α5β1 antagonist, caused significant suppression of choroidal neovascularization; the area of neovascularization was reduced by 33 to 40%. When an osmotic pump delivering 10 μg/h of JSM6427 was implanted 7 days after rupture of Bruch's membrane, there was terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining in vascular cells within the neovascularization and significant regression of the neovascularization over the next week. JSM6427 also induced apoptosis of cultured vascular endothelial cells. Fibronectin stimulates phosphorylation of extracellular signal-regulated kinase (ERK) in α5β1-expressing cells that is blocked by JSM6427. These data suggest that α5β1 plays a role in the development and maintenance of choroidal neovascularization and provides a target for therapeutic intervention.

  • Received November 18, 2005.
  • Accepted March 9, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (6)
Molecular Pharmacology
Vol. 69, Issue 6
1 Jun 2006
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Research ArticleArticle

Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an α5β1 Integrin Antagonist

Naoyasu Umeda, Shu Kachi, Hideo Akiyama, Grit Zahn, Doerte Vossmeyer, Roland Stragies and Peter A. Campochiaro
Molecular Pharmacology June 1, 2006, 69 (6) 1820-1828; DOI: https://doi.org/10.1124/mol.105.020941

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Research ArticleArticle

Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an α5β1 Integrin Antagonist

Naoyasu Umeda, Shu Kachi, Hideo Akiyama, Grit Zahn, Doerte Vossmeyer, Roland Stragies and Peter A. Campochiaro
Molecular Pharmacology June 1, 2006, 69 (6) 1820-1828; DOI: https://doi.org/10.1124/mol.105.020941
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