Pathogenesis of retinopathy of prematurity

Growth Horm IGF Res. 2004 Jun;14 Suppl A:S140-4. doi: 10.1016/j.ghir.2004.03.030.

Abstract

Retinopathy of prematurity (ROP) is a major cause of blindness in children in developed countries. ROP is a two-phase disease, beginning with delayed retinal vascular growth after premature birth (Phase I). Phase II follows when Phase I-induced hypoxia releases factors to stimulate new blood vessel growth. Both oxygen-regulated and non-oxygen-regulated factors contribute to normal vascular development and retinal neovascularization. Vascular endothelial growth factor (VEGF) is an important oxygen-regulated factor. A critical non-oxygen-regulated growth factor is insulin-like growth factor-I (IGF-I). In knockout mice, lack of IGF-I prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro, low IGF-I levels prevent VEGF-induced activation of Akt, a kinase critical for vascular endothelial cell survival. We found that premature infants who develop ROP have low levels of serum IGF-I compared to age-matched infants without disease. IGF-I is critical to normal vascular development. Low IGF-I predicts ROP in premature infants, and restoration of IGF-I to normal levels might prevent ROP.

Publication types

  • Review

MeSH terms

  • Animals
  • Human Growth Hormone / metabolism
  • Humans
  • Infant, Newborn
  • Infant, Premature*
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • Mice
  • Mice, Knockout
  • Neovascularization, Pathologic
  • Retinopathy of Prematurity / metabolism
  • Retinopathy of Prematurity / physiopathology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • Human Growth Hormone
  • Insulin-Like Growth Factor I