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Tejas Kumar, Laura Ah-Kye, Samantha Dando, Senthil Selvam, Marcus Fruttiger, Paul McMenamin; Characterisation of VEGF in a new model of oxygen-induced vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3445.
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© ARVO (1962-2015); The Authors (2016-present)
Despite intense research using animal models, the pathophysiology of retinopathy of prematurity (ROP), especially in the severe stages, remains incompletely understood. We recently developed a mouse model of oxygen-induced vitreoretinopathy (McMenamin et al, IOVS, in press) in which mice are exposed to hyperoxia from postnatal day (P) 0-7, recapitulating several aspects of severe human ROP. In the present study, we characterised the effects of P0-P7 hyperoxia exposure on retinal vasculature at P7, P14 and P21, and hypothesised that after removal from hyperoxia, retinal VEGF expression would be upregulated.
C57BL/6 mice (n=38) were randomised into two groups: A) Normoxia (control), B) 75% O2 P0-P7. At P7, P14 or P21 mice were humanely killed and retinas were either fixed for microscopy or snap-frozen for relative quantification of VEGF expression using qPCR. Blood vessels were visualised using Isolectin B4 staining and retinal avascularity (%) was calculated using Image J software. Values are expressed as mean±SD.
At P7, vessels were observed at the retinal periphery, however the retina was largely avascular (90.5±4.0%), significantly more than control mice (5.6±2.0%, p<0.0001). Retinal VEGF expression in hyperoxia and control groups at P7 was similar. At P14, vascularisation was observed at the periphery and optic disc in experimental mice, but total retinal avascularity remained significantly higher than controls (70.0±13.9% vs 1.2±0.3%, p<0.0001). This was accompanied by a 2.3-fold increase in retinal VEGF mRNA levels compared to controls (p<0.0001). At P21 tortuous vessels extended from the optic disc towards the periphery and retinal avascularity remained significantly higher in experimental mice (30.4±9.6%) compared to controls (1.1±0.44%, p<0.0001). VEGF mRNA expression in experimental mice had returned to control levels by P21. Neovascular tuft formation was not observed and hyaloid vasculature persisted across all time points in this new model.
Early exposure to hyperoxia significantly inhibits vascular growth in the retina. The concomitant increase in vessel growth and VEGF expression at P14 suggests that VEGF may drive vascularisation in this novel model and contribute to its pathogenesis. However, it does not drive neovascular tuft formation as it does in the conventional OIR P7-P12 model. Persistence of hyaloid vessels may have a role in modulating VEGF expression.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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