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

Proc Natl Acad Sci U S A. 2001 May 8;98(10):5804-8. doi: 10.1073/pnas.101113998. Epub 2001 May 1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Survival*
  • DNA Primers
  • Endothelial Growth Factors / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Infant, Newborn
  • Insulin-Like Growth Factor I / metabolism*
  • Lymphokines / metabolism*
  • Retinal Vessels / cytology
  • Retinal Vessels / metabolism*
  • Retinopathy of Prematurity / metabolism*
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • DNA Primers
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Insulin-Like Growth Factor I