Document Detail


Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: direct correlation with clinical retinopathy of prematurity.
MedLine Citation:
PMID:  11331770     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
A Hellstrom; C Perruzzi; M Ju; E Engstrom; A L Hard; J L Liu; K Albertsson-Wikland; B Carlsson; A Niklasson; L Sjodell; D LeRoith; D R Senger; L E Smith
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2001-05-01
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  98     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2001 May 
Date Detail:
Created Date:  2001-05-10     Completed Date:  2001-06-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5804-8     Citation Subset:  IM    
Affiliation:
Department of Clinical Neuroscience, Section of Ophthalmology, and International Pediatric Growth Research Center, The Queen Silvia Children's Hospital, 41685 Göteborg, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cell Survival*
DNA Primers
Endothelial Growth Factors / metabolism*
Endothelium, Vascular / cytology,  metabolism*
Humans
Infant, Newborn
Insulin-Like Growth Factor I / metabolism*
Lymphokines / metabolism*
Retinal Vessels / cytology,  metabolism*
Retinopathy of Prematurity / metabolism*
Signal Transduction*
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Endothelial Growth Factors; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 67763-96-6/Insulin-Like Growth Factor I
Comments/Corrections

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