QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.020941v1 69/6/1820    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Umeda, N. Articles by Campochiaro, P. A. Search for Related Content PubMed PubMed Citation Articles by Umeda, N. Articles by Campochiaro, P. A.

Suppression and Regression of Choroidal Neovascularization by Systemic Administration of an ₅₁ Integrin Antagonist

Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland (N.U., H.A., P.A.C.); and Jerini Pharmaceuticals, Berlin, Germany (G.Z., D.V., R.S.)

Integrin ₅₁ 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 ₅₁ 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 ₅₁ 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 ₅₁-expressing cells that is blocked by JSM6427. These data suggest that ₅₁ plays a role in the development and maintenance of choroidal neovascularization and provides a target for therapeutic intervention.

Address correspondence to: Dr. Peter A. Campochiaro, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287-9277. E-mail: pcampo{at}jhmi.edu

This article has been cited by other articles:

				B. Xie, J. Shen, A. Dong, M. Swaim, S. F. Hackett, L. Wyder, S. Worpenberg, S. Barbieri, and P. A. Campochiaro An Adam15 amplification loop promotes vascular endothelial growth factor-induced ocular neovascularization FASEB J, August 1, 2008; 22(8): 2775 - 2783. [Abstract] [Full Text] [PDF]

				Y. Fu, M. L. Ponce, M. Thill, P. Yuan, N. S. Wang, and K. G. Csaky Angiogenesis Inhibition and Choroidal Neovascularization Suppression by Sustained Delivery of an Integrin Antagonist, EMD478761 Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 5184 - 5190. [Abstract] [Full Text] [PDF]

				T. Dietrich, J. Onderka, F. Bock, F. E. Kruse, D. Vossmeyer, R. Stragies, G. Zahn, and C. Cursiefen Inhibition of Inflammatory Lymphangiogenesis by Integrin {alpha}5 Blockade Am. J. Pathol., July 1, 2007; 171(1): 361 - 372. [Abstract] [Full Text] [PDF]