September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
A novel mouse model of hyperoxia-induced retinopathy that mimics pathognomonic features of severe retinopathy of prematurity (ROP) in humans
Author Affiliations & Notes
  • Paul G McMenamin
    Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia
  • Rachel Kenny
    Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia
  • Cecilia Naranjo Golborne
    Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia
  • Jeremiah Lim
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Bang V Bui
    Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Paul McMenamin, None; Rachel Kenny, None; Cecilia Naranjo Golborne, None; Jeremiah Lim, None; Bang Bui, None
  • Footnotes
    Support  Jean and Julias Tahija Foundation, National Health and Medical Research Council of Australia
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6260. doi:
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      Paul G McMenamin, Rachel Kenny, Cecilia Naranjo Golborne, Jeremiah Lim, Bang V Bui; A novel mouse model of hyperoxia-induced retinopathy that mimics pathognomonic features of severe retinopathy of prematurity (ROP) in humans. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6260.

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

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Abstract

Purpose : The popular ‘oxygen-induced retinopathy’ mouse model (75% oxygen between postnatal days 7-12 [P7-12]) has been extensively used to study the vascular changes in the retina that result from exposure to hyperoxia followed by a return to room air. However, in this model the retina and its vasculature assumes normal morphology after 5-6 weeks. The aim of the present study was to develop a mouse model of hyperoxia-induced retinopathy that reproduced important key clinical, functional, histological and vascular features of untreated severe ROP in humans.

Methods : C57Bl/6J mice exposed to 65% oxygen from P0-7 mice (n=75) were investigated clinically using fluorescein angiography, optical coherence tomography (OCT), and electroretinography (ERG) at various time points between 3 weeks (w) to 40w. Histopathology, frozen section immunostaining and wholemount lectin staining of the retinal vasculature was undertaken at 3w, 5w, 8w, 20w and 40w. Controls (n=59) were exposed to normal air.

Results : At 3w, significant vitreous hemorrhages and persistence hyaloid vessels were observed in hyperoxia-exposed mice. Compared to controls, hyaloid and retinal vessels showed significantly increased tortuosity (p<0.05), which persisted until 40w. Following hyperoxia exposure retinal vascularization remained incomplete up to 40w and intraretinal capillary plexi were abnormal, particularly in peripheral zones. ERG studies showed a significant decrease in photoreceptor (a-wave), bipolar cell (b-wave), amacrine cell and ganglion cell function in P0-7 hyperoxia-exposed mice at 8w (p<0.01). All components of the ERG remain significantly attenuated at 20w of age (p<0.01); however, ganglion cell function was significantly more affected (p<0.05). Vitreal membranes associated with retinal detachments were collagen type IV+ and alpha smooth muscle actin+. Abnormal hyaloid vessels and capillaries of the tunica vasculosa lentis persisted in hyperoxia-exposed eyes upto 40w of age.

Conclusions : Hyperoxia exposure between P0-7 resulted in several long-term changes that closely resembled severe ROP in humans. This model will prove useful in testing the safety and efficacy of potential interventions in humans such as anti-VEGF therapy.

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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