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.