Pathogenesis of retinopathy of prematurity.
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.
Smith
Lois E H
LE
Department of Ophthalmology, Children's Hospital, Harvard Medical School, Boston, MA 02153, USA. Lois.Smith@tch.harvard.edu
D000818:Animals; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D012178:Retinopathy of Prematurity / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I