June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Validation and Characterization of Murine Oxygen-induced Retinopathy of Prematurity Model
Author Affiliations & Notes
  • Yubin Qiu
    Novartis, cambridge, MA
  • Amber Woolfenden
    Novartis, cambridge, MA
  • Wei Zheng
    Novartis, cambridge, MA
  • Karen Anderson
    Novartis, cambridge, MA
  • Melinda Hubbard
    Novartis, cambridge, MA
  • John Demirs
    Novartis, cambridge, MA
  • Joseph Loureiro
    Novartis, cambridge, MA
  • Joy Ghosh
    Novartis, cambridge, MA
  • Stephen Poor
    Novartis, cambridge, MA
  • Bruce Jaffee
    Novartis, cambridge, MA
  • Footnotes
    Commercial Relationships Yubin Qiu, Novartis (E); Amber Woolfenden, Novartis Institutes for Biomedical Research (E); Wei Zheng, Novartis (E); Karen Anderson, Novartis (E); Melinda Hubbard, Novartis Institutes of Biomedical Research (E); John Demirs, Novartis Institutes for Biomedical Research, Inc. (E); Joseph Loureiro, novartis (E); Joy Ghosh, Novartis (E); Stephen Poor, Novartis Institue of Biomedical Research (E); Bruce Jaffee, Novartis (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 617. doi:https://doi.org/
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      Yubin Qiu, Amber Woolfenden, Wei Zheng, Karen Anderson, Melinda Hubbard, John Demirs, Joseph Loureiro, Joy Ghosh, Stephen Poor, Bruce Jaffee; Validation and Characterization of Murine Oxygen-induced Retinopathy of Prematurity Model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):617. doi: https://doi.org/.

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

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Abstract

Purpose: The mouse oxygen-induced retinopathy model is widely used to investigate the mechanism and treatment of proliferative ocular angiogenesis. The purpose of this study is to characterize the growth of retinal neovascularization (RNV) in response to oxygen treatment, to establish a positive control for the inhibition of RNV for future compound testing and to explore the mechanism of ocular angiogenesis.

Methods: C57/Bl6 mice dams were exposed to 75% oxygen from postnatal day (P) 7 to P12. Eyes were harvested and fixed at P17. To identify vasculature, retinas were stained with Isolectin B4-594. Fluorescent images of the tissue were captured and RNV areas were quantified with AxioVision software. In addition, eyes were freshly frozen in OCT for IHC. Fluorescein angiography was performed in P17 pups. Pups were anesthetized, and images were acquired after intraperitoneal (IP) injection of sodium fluorescein with a MicronIII lens and StreamPix5 single Camera Program from Phoenix Research Laboratories, Inc. In the efficacy studies, pups were treated at P12 and P14 via IP injection with an anti-VEGF antibody (12 pups) or negative control (12 pups). Inter-group differences were compared by one-way analysis of variance (ANOVA) with a Neuman-keuls post hoc analysis. For the characterization study, retinas were collected at P5, P8, P12, P13, P15, P17 and P19. Retinas from each mouse were pooled as one sample and 6 samples per condition were assessed for mRNA expression. At P17, 4 retinas were pooled for VEGF protein analysis using Elisa. The mRNA expression profile was evaluated with microarray analysis and genes with altered expression were confirmed with a TaqMan assay.

Results: Hyperoxia results in retinal vessel loss and subsequent RNV, vessel tortuosity, and leakage. RNV growth was dose dependently inhibited by 44% and 89% with anti-VEGF antibody treatment at 3 mg/kg and 10 mg/kg, respectively. In this model, VEGF protein levels are elevated ~ 4 fold at P17; the expression profiles of many known genes, such as VEGFa, VEGFR, PDGFb, Ang2 and EPO, as well as genes without annotation were significantly up-regulated.

Conclusions: RNV was induced under hypoxia conditions. Anti-VEGF antibody can inhibit RNV growth in a dose dependent manner and therefore can be used as a positive control in this model. Genes expression profile changes may be used as biomarkers to study the mechanism of retinal angiogenesis.

Keywords: 499 diabetic retinopathy • 706 retinopathy of prematurity • 609 neovascularization  
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