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Blood, 1 December 2005, Vol. 106, No. 12, pp. 3831-3838. Prepublished online as a Blood First Edition Paper on August 25, 2005; DOI 10.1182/blood-2005-03-0889. This Article Full Text (PDF) All Versions of this Article: 2005-03-0889v1 106/12/3831    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Economopoulou, M. Articles by Chavakis, T. Search for Related Content PubMed PubMed Citation Articles by Economopoulou, M. Articles by Chavakis, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 3, 2005 Accepted August 15, 2005 Inhibition of pathological retinal neovascularization by -defensins Matina Economopoulou, Khalil Bdeir, Douglas B Cines, Franz Fogt, Yasmina Bdeir, Jacek Lubkowski, Wuyuan Lu, Klaus T Preissner, Hans P Hammes, and Triantafyllos Chavakis* Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA; Department of Internal Medicine V, University Clinic Mannheim, Mannheim, Germany; Department of Ophthalmology, Justus-Liebig-University, Giessen, Giessen, Germany Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA Macromolecular Assembly Structure and Cell Signaling Section, National Cancer Institute, Frederick, MD, USA Institute of Human Virology, University of Maryland Biotechnology Institute, Baltimore, MD, USA Institute for Biochemistry, Justus-Liebig-University, Giessen, Giessen, Germany Department of Internal Medicine V, University Clinic Mannheim, Mannheim, Germany Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD, USA * Corresponding author; email: chavakist{at}mail.nih.gov. Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells, and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components like fibronectin (FN). Recently, we demonstrated that -defensins interfere with 51-FN interactions and dependent endothelial cell functions. Here, -defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, -defensins specifically inhibited 51-integrin dependent migration of bovine retinal endothelial cells (BREC) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in three-dimensional fibrin-matrices. An upregulation of 1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and ocular administration of -defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of 51-blocking antibody. -defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that -defensins inhibit pathological retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y.-s. Wang, D. Li, H.-s. Shi, Y.-j. Wen, L. Yang, N. Xu, X.-c. Chen, X. Chen, P. Chen, J. Li, et al. Intratumoral Expression of Mature Human Neutrophil Peptide-1 Mediates Antitumor Immunity in Mice Clin. 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