Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

Proceedings of the National Academy of Sciences of the United States of America - Tập 98 Số 10 - Trang 5804-5808 - 2001
Ann Hellström1, Carole Perruzzi1, Meihua Ju1, Eva Engström1, Jun‐Li Liu1, Kerstin Albertsson‐Wikland1, Björn Carlsson1, Aimon Niklasson1, Lena Sjödell1, Derek LeRoith1, Donald R. Senger1, Lois E.H. Smith1
1Department of Clinical Neuroscience, Section of Ophthalmology, and International Pediatric Growth Research Center, Department of Pediatrics, The Queen Silvia Children's Hospital, 41685 Göteborg, Sweden; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215; Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02115; Endocrine Branch, National Institutes of Health, Bethesda, MD 20892; and Research Centre for Endocrinology and...

Tóm tắt

Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro , low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can predict which infants will develop retinopathy of prematurity and further suggests that early restoration of IGF-I in premature infants to normal levels could prevent this disease.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 98 Số 10

5804-5808

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