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

被引:432
作者
Hellstrom, A
Perruzzi, C
Ju, MH
Engström, E
Hård, AL
Liu, JL
Albertsson-Wikland, K
Carlsson, B
Niklasson, A
Sjödell, L
LeRoith, D
Senger, DR
Smith, LEH
机构
[1] Harvard Univ, Dept Ophthalmol, Sch Med, Childrens Hosp, Boston, MA 02115 USA
[2] Queen Silvia Childrens Hosp, Sect Opthalmol, Dept Clin Neurosci, S-41685 Gothenburg, Sweden
[3] Queen Silvia Childrens Hosp, Dept Pediat, Int Pediat Growth Res Ctr, S-41685 Gothenburg, Sweden
[4] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA
[5] NIH, Endocrine Branch, Bethesda, MD 20892 USA
[6] Univ Goteborg, Dept Internal Med, Res Ctr Endocrinol & Metab, S-41345 Gothenburg, Sweden
关键词
D O I
10.1073/pnas.101113998
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 revels 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 ICF-I increases to a critical lever, retinal neovascularization is triggered. These data indicate that serum LCF-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 levers could prevent this disease.
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收藏
页码:5804 / 5808
页数:5
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