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Horm Metab Res 2001; 33(5): 307-311
DOI: 10.1055/s-2001-15279
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Topical Application of Integrin Antagonists Inhibits Proliferative Retinopathy

B. Riecke1 , E. Chavakis1 , R. G. Bretzel1 , T. Linn1 , K. T. Preissner2 , M. Brownlee3 , H.-P. Hammes1,4
  • 1 3rd Medical Department, Justus-Liebig-University Giessen, Germany
  • 2 Institute for Biochemistry, Justus-Liebig-University Giessen, Germany
  • 3 Albert Einstein College of Medicine, Diabetes Research Center, Bronx, New York, NY, USA
  • 4 5th Medical Department, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany
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Publication History

Publication Date:
31 December 2001 (online)

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The expression of αv-integrins is highly selective for angiogenic endothelial cells; ligation inhibition by cyclic RGD peptides prevents pathological neovascularization in tumor or retinopathy models to a large extent. We have previously demonstrated that proliferative retinopathy in a mouse model of retinopathy of prematurity (ROP model) can be reduced by more than 70 %. To minimize systemic side effects and unwanted interference with responsive angiogenesis, we investigated topical application of cyclic RGD-peptides. In preliminary experiments, we could exclude any inhibiting effects of the carrier solution containing EDTA, Na2S, mannitol, hydroxyethyl starch, and benzalconium chloride on the inhibitory effect of cyclic RGD peptides. Retinal presence of small molecular-mass integrin antagonists after topical application was confirmed using fluorescein-labeled cyclic RGD peptide. Topical application of the peptide to the eye inhibited proliferative retinopathy in a dose-dependent fashion with a maximum of almost 50 %. These results suggest that small molecular-mass peptide antagonists of αv-type integrins are efficient in inhibiting proliferative retinopathy by topical application.

Key words:

Diabetic Retinopathy - Angiogenesis - αv-type Integrins - RGD Peptides

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H.-P.  Hammes, M.D.

5th Medical Department
University Hospital Mannheim
University of Heidelberg

68167 Mannheim
Germany


Phone: Phone:+ 49 (621) 383-2663

Fax: Fax:+ 49 (621) 383-3804

Email: E-mail:hans-peter.hammes@med5.ma.uni-heidelberg.de

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