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Tom A. Drixler, Inne H. M. Borel Rinkes, Ewan D. Ritchie, Frits W. Treffers, Theo J. M. V. van Vroonhoven, Martijn F. B. G. Gebbink, Emile E. Voest; Angiostatin Inhibits Pathological but Not Physiological Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2001;42(13):3325-3330.
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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
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