Document Detail


The relationship of retinal VEGF and retinal IGF-1 mRNA with neovascularization in an acidosis-induced model of retinopathy of prematurity.
MedLine Citation:
PMID:  16500767     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR. METHODS: Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR). RESULTS: Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls. CONCLUSIONS: In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis.
Authors:
David A Leske; Jianmin Wu; Martina Mookadam; Yi Chen; Michael P Fautsch; Jonathan M Holmes; William L Lanier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current eye research     Volume:  31     ISSN:  0271-3683     ISO Abbreviation:  Curr. Eye Res.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-27     Completed Date:  2006-04-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8104312     Medline TA:  Curr Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  163-9     Citation Subset:  IM    
Affiliation:
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
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MeSH Terms
Descriptor/Qualifier:
Acidosis / chemically induced,  metabolism*
Ammonium Chloride / toxicity
Animals
Animals, Newborn
Disease Models, Animal
Female
Gene Expression Regulation / physiology*
Humans
Infant, Newborn
Insulin-Like Growth Factor I / genetics*
Pregnancy
RNA, Messenger / metabolism*
Rats
Rats, Sprague-Dawley
Retinal Neovascularization / metabolism*
Retinopathy of Prematurity / chemically induced,  metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Vascular Endothelial Growth Factor A / genetics*
Grant Support
ID/Acronym/Agency:
EY12798/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/RNA, Messenger; 0/Vascular Endothelial Growth Factor A; 0/vascular endothelial growth factor A, rat; 12125-02-9/Ammonium Chloride; 67763-96-6/Insulin-Like Growth Factor I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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