Angiostatin Inhibits Pathologic Neovascularization in a Mouse Model of Ischemic Retinopathy

Abstract

Abstract: : Purpose: To study the efficacy of angiostatin on normal and abnormal angiogenesis in a newborn mouse model of ischemic retinopathy. Methods: Oxygen–induced retinopathy was induced by subjecting postnatal day 7 (P7) mice to 73% +/– 2% oxygen (5 days) followed by normoxic conditions (relative hypoxia) for another 5 days. Purified human angiostatin was intravitreally injected into one eye of mice on P17. The pattern of retinal blood vasculature was visualized by Chinese traditional ink perfusion whole–mounted retinae on day 17 and 22. Retinal neovasularization was evaluated by the number of endothelial cell nuclei above the inner limiting membrane in P17 and P22 eye sections. Results: P17 whole–mounted retinae showed relative hypoxia resulted in pathologic angiogenesis from the peripheral retinal vessels but no normal branches originated from the major vessels. This abnormal proliferation was significantly inhibited 5 days after introduction of angiostatin; however the physiological retinal angiogenesis of the central area was unaffected. The number of vascular endothelial cell nuclei above the inner limiting membrane in eyes treated with angiostatin was reduced 68% compared to the fellow (control) eyes (p<0.001). Conclusions: Angiostatin inhibits oxygen–induced pathologic retinal neovascularization without affecting physiological retinal angiogenesis in newborn mice.

Keywords: neovascularization • diabetic retinopathy • age-related macular degeneration