Volume 21, Issue 12 p. 3272-3278
Research Communication
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Treatment of hypoxia-induced retinopathy with targeted proapoptotic peptidomimetic in a mouse model of disease

Johanna Lahdenranta

Johanna Lahdenranta

The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA

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Richard L. Sidman

Richard L. Sidman

Harvard Medical School and Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts, USA

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Renata Pasqualini

Corresponding Author

Renata Pasqualini

The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA

Correspondence: The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. E-mail: [email protected] or [email protected]Search for more papers by this author
Wadih Arap

Corresponding Author

Wadih Arap

The University of Texas, M. D. Anderson Cancer Center, Houston, Texas, USA

Correspondence: The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA. E-mail: [email protected] or [email protected]Search for more papers by this author
First published: 18 May 2007
Citations: 24

ABSTRACT

We have previously identified ligands from combinatorial peptide libraries that target tumor vasculature after in vivo selection. These ligands bind to differentially expressed receptors in angiogenic vascu-lature such as αvβ3vβ5 integrins, aminopeptidase N, and aminopeptidase A. We hypothesized that we can use these ligands to target angiogenic vasculature in retinopathies. Pathological retinal angiogenesis in conditions such as diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration is a major cause of blindness for which current treatments are inadequate. Here we tested whether known tumor vasculature targeting peptide ligands displayed on bac-teriophage particles would home to the proliferating blood vessels of the retina in a standard mouse model of retinopathy of prematurity. We found that activated retinal blood vessels share many of the endothelial and periendothelial cell receptors expressed in tumor vas-culature. Furthermore, these vascular receptors—αv integrins and aminopeptidases—are accessible through the circulation and mediate phage homing and internal-ization to endothelial and periendothelial cells. Treatment of mice with a peptide containing a αvβ3vβ5-integrin targeting domain fused to a proapoptotic domain significantly reduced oxygen-induced retinal angiogenesis by selectively inducing activated endothe-lial cell apoptosis. Targeted proapoptotic peptides may prove useful in the management of angiogenic retinal diseases.—Lahdenranta J., Sidman, R. L., Pasqualini, R., Arap W. Treatment of hypoxia-induced retinopathy with targeted proapoptotic peptidomimetic in a mouse model of disease. FASEB J. 21, 3272–3278 (2007)