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M Elizabeth Hartnett, Yanchao Jiang, Merica Hale, Haibo Wang, George W. Smith, Robert Lane; Intrauterine Growth Restriction Alters Retinal IGF-1 Levels in Newborn Rats. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3993.
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Intrauterine growth restriction (IUGR) causes poor postnatal weight gain, which has been associated with low serum insulin-like growth factor-1 (IGF-1) and severe ROP in human infants. Still, the link between IUGR and ROP and mechanism for this observation remain unknown. We used a rat model of IUGR to test the hypothesis that IUGR affects retinal IGF-1 and receptor (IGF-1R) expression.
Prenatal bilateral ligation of the uterine arteries in timed pregnant dams induced uteroplacental insufficiency and IUGR in pups. Controls were dams placed under anesthesia without artery ligation. Two days following surgery, postnatal day (p)0 pups were delivered by Caesarian section. Pup retinas were dissected for growth factor mRNA or protein for IGF-1, IGF1-binding protein 3 (IGF-1BP3), IGF-1R, vascular endothelial growth factor (VEGF) and receptor 1 (VEGFR1), or flat mount labeling of the inner vascular plexus by lectin or ADPase.
At p0, the inner retina was 4.5% vascularized. ADPase labeled cells preceded obvious blood vessels in both IUGR-induced and control pups. There were no differences in lectin stained retinal vascular/total areas between IUGR induced pups and controls (p=0.65). In IUGR induced male pups, there was significantly increased IGF-1 (p=.02) and IGF-1BP3 (p=0.01) mRNAs, whereas both male and female pups had reduced IGF-1R protein (p<0.05).
IUGR induced changes in IGF-1 and IGF-1R differentially in males and females, but did not affect VEGF or VEGFR1 expression or early inner plexus vascularization. Further studies are warranted to determine potential effects of IUGR on retinal angiogenesis and ROP.
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