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Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor–type integrins inhibits retinal neovascularization

Nature Medicine volume 2, pages 529–533 (1996)Cite this article

Abstract

Retinal neovascularization is a major cause of blindness in such disorders as retinopathy of prematurity, proliferative diabetic retinopathy and senile macular degeneration. Because ligation of vitronectin receptor–type integrins appears to be required for the survival and maturation of newly formed but not quiescent blood vessels in several vascular beds including the retina, blockade of this downstream adhesion receptor system was investigated. In a mouse model of hypoxia–induced retinal neovascularization twice daily administration of 1 to 20 mg cyclic αv–integrin antagonist peptide per kilogram of body weight reduced capillary proliferation in a dose–dependent fashion — maximum 76% — without obvious side effects. A cyclic control peptide displayed no inhibitory effect on neovascularization. These findings indicate that systemic application of vitronectin receptor antagonists appears to be clinically feasible and is efficient in preventing retinal neovascularization and superior to cytokine–blocking strategies.

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Author notes

  1. Hans-Peter Hammes and Michael Brownlee: These authors contributed equally to this work.

Authors and Affiliations

  1. Third Department Internal Medicine, Medizinische Klinik und Poliklinik, Justus-Liebig-Universität, Rodthohl 6, D-35385, Giessen, Germany

    Hans-Peter Hammes

  2. Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, New York, 10461, USA

    Michael Brownlee

  3. Merck KGaA, D-64293, Darmstadt, Germany

    Alfred Jonczyk & Arne Sutter

  4. Haemostasis Research Unit, MPI, Kerckhoff-Klinik, D-61231, Bad Nauheim, Germany

    Klaus T. Preissner

Authors
  1. Hans-Peter Hammes
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  2. Michael Brownlee
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  3. Alfred Jonczyk
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  4. Arne Sutter
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  5. Klaus T. Preissner
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Hammes, HP., Brownlee, M., Jonczyk, A. et al. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor–type integrins inhibits retinal neovascularization. Nat Med 2, 529–533 (1996). https://doi.org/10.1038/nm0596-529

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