Pathogenesis of retinopathy of prematurity.
Retinopathy of prematurity (ROP) is a blinding disease, initiated by delayed retinal vascular growth after premature birth. There are both oxygen-regulated and non-oxygen-regulated factors, which contribute to both normal vascular development and retinal neovascularization. One important oxygen-regulated factor, critical to both phases of ROP, is vascular endothelial growth factor (VEGF). A critical non oxygen-regulated growth factor is insulin-like growth factor (IGF-1). In knockout mice, lack of IGF-1 prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro, low IGF-1 prevents vascular endothelial growth factor-induced activation of Akt, a kinase critical for vascular endothelial cell survival. Premature infants who develop ROP have lower levels of serum IGF-1 than age-matched infants without disease.


CONCLUSIONS
IGF-1 is critical to normal vascular development. Low IGF-1 predicts ROP and restoration of IGF-1 to normal levels may prevent ROP.
Department of Ophthalmology, Children's Hospital, Harvard Medical School, 300 Longwood Drive, Boston, MA 02115, USA. lois.smith@tch.harvard.edu
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Smith
D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000032:analysis / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011379:Prognosis; D012171:Retinal Vessels / Q000378:metabolism / Q000503:physiopathology; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000503:physiopathology*; D012307:Risk Factors
D016228:Endothelial Growth Factors; D007334:Insulin-Like Growth Factor I