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(Investigative Ophthalmology and Visual Science. 2001;42:3325-3330.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Angiostatin Inhibits Pathological but Not Physiological Retinal Angiogenesis

Tom A. Drixler1,2, Inne H. M. Borel Rinkes1,2, Ewan D. Ritchie1, Frits W. Treffers3, Theo J. M. V. van Vroonhoven1, Martijn F. B. G. Gebbink2 and Emile E. Voest2

1 From the Department of Surgery; the 2 Laboratory of Medical Oncology, Division of Medical Oncology; and the 3 Donders Institute of Ophthalmology, University Medical Center, Utrecht, The Netherlands.

PURPOSE. Antiangiogenic treatment is a promising new therapy for angiogenesis-dependent diseases. In the current study, the biologic effects on pathologic and physiological angiogenesis in the retina of angiostatin, a very potent angiogenesis inhibitor were determined. In addition, the effects of angiostatin on the growth and development of newborn mice were examined.

METHODS. Oxygen-induced retinopathy was induced by subjecting mice postnatal day (P)7 to hyperoxic conditions (5 days) followed by normoxic conditions (relative hypoxia). Mice were treated with angiostatin (intravitreal or systemic). Retinal blood vessels were visualized by fluorescein angiography. Retinal neovascularization was assessed by counting intravitreal endothelial cell nuclei. Growth and organogenesis were determined between P0 and P14.

RESULTS. Relative hypoxia resulted in intravitreal proliferation of retinal blood vessels. However, proliferation was inhibited completely by systemic administration of angiostatin without affecting normal retinal vascularization. After intravitreal injection of angiostatin, pathologic proliferation of the retinal blood vessels was impaired by 62%. Neither systemic nor intravitreal treatment impaired the development or growth of organs throughout the body.

CONCLUSIONS. Angiostatin inhibits oxygen-induced intravitreal pathologic retinal angiogenesis without affecting the development of physiological retinal vascularization, development, and growth of newborn mice. Therefore, antiangiogenic treatment may be a useful tool in the treatment of proliferative retinopathies.




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