September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Neovascular changes and angiogenic factor production during combined intrauterine growth restriction and oxygen-induced retinopathy
Author Affiliations & Notes
  • Silke Becker
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Haibo Wang
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Baifeng Yu
    Department of Neonatology, University of Utah, Salt Lake City, Utah, United States
  • Robert H Lane
    Children's Hospital of Wisconsin, Wilwaukee, Wisconsin, United States
  • M Elizabeth Hartnett
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Silke Becker, None; Haibo Wang, None; Baifeng Yu, None; Robert Lane, None; M Elizabeth Hartnett, None
  • Footnotes
    Support  National Institutes of Health EY014800, R01 R01EY015130 and R01EY017011, March of Dimes 6-FY13-75, Unrestricted Grant from Research to Prevent Blindness, Inc., New York, NY
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3642. doi:
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    • Get Citation

      Silke Becker, Haibo Wang, Baifeng Yu, Robert H Lane, M Elizabeth Hartnett; Neovascular changes and angiogenic factor production during combined intrauterine growth restriction and oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3642.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Preterm neonates with intrauterine growth restriction (IUGR) have low circulating insulin-like growth factor-1 (IGF-1) and are at increased risk of retinopathy of prematurity (ROP). To address whether IUGR is a risk factor for ROP and investigate the relationship with angiogenic factors, we developed a rat model combining IUGR with oxygen-induced retinopathy (OIR). We studied features of OIR (avascular area (AVA) and intravitreal neovascularization (IVNV)) and serum angiogenic factors.

Methods : IUGR was induced by bilateral uterine artery ligation at embryonic day 19.5 in Sprague Dawley rats. Controls dams received anaesthesia (sham). Pups were assigned to sham (birth weight >6g; n=23) or IUGR groups (birth weight ≤6g; n=34). Litters were maintained at 12-16 pups and transferred into an OxyCycler within 4-6 hours of birth. Pups were exposed to O2 concentrations of 50% for 48 hours, cycled between 10% and 50% every 24 hours until postnatal day 15 and placed into room air until day 18. AVA and IVNV were determined by retinal flatmount and serum vascular endothelial growth factor (VEGF), IGF-1 and erythropoietin (EPO) measured by ELISA. Data are expressed as means ± SEM and statistical analysis was performed by t-test.

Results : Weight gain until day 18 was similar in IUGR (14.6±0.5g) compared to sham (14.6±0.7g). AVA was reduced in IUGR (23.0±2.0%) versus sham (41.5±2.5%, P=0.002), with no difference between males and females. IVNV was reduced in IUGR (2.3±0.3%) compared to sham (4.1±0.6%, P<0.0001) and tended to be smaller in IUGR males (1.8±0.3%) than females (2.6±0.4%, P=0.133). Neither serum VEGF nor serum IGF-1 was significantly different between IUGR and sham OIR at the time point measured. However, EPO was increased in males with IUGR (104.2±8.3pg/mL) compared to sham (48.5±10.2 pg/mL, P=0.014), but decreased in females with IUGR (69.4±16.7pg/mL) compared to sham (158.0±33.0 pg/mL, P=0.038) at p18.

Conclusions : Both AVA and IVNV were reduced in IUGR compared to sham, suggesting a protective effect on OIR. IUGR decreased EPO in serum during OIR in females, whereas EPO was increased in males, suggesting a sex-based difference in circulating growth factor expression. Further studies are warranted to understand the mechanisms for reduced IVNV in males with greater EPO expression.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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