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Y. Feng, S. Gross, H.-P. Hammes; Development of Capillary Network Despite Persistent Hyperoxia in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):54.
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Oxygen regulates vessel growth in the retina both in physiological and pathological angiogenesis. Hyperoxia and hypoxia contribute to retinal vasoregression and neovascularisation, respectively. However, we occasionally observed an outgrowth of deep capillary layer during hyperoxia in a mouse model of oxygen-induced retinopathy (OIR). The aim of the current study was to investigate this escape effect by using long-term hyperoxia and its outcome on intraretinal angiogenesis in the developing mouse retina.
Mice in the conventional OIR model at p17 (5 days of hyperoxia plus 5 days of hypoxia) and in the modified OIR mouse model at p17 (10 days of hyperoxia) were used for the study. PAS staining on paraffin sections was performed to determine the location of neovascularization in prolonged hyperoxia. Outgrowth of deep capillary layers, avascular zone and neovascular tufts were quantitated in whole mount retinas stained with collagen IV.
Mice in the modified OIR model with prolonged hyperoxia did not show any preretinal neovascularization, whereas mice in the conventional OIR model demonstrated numerous preretinal neovascular tufts at p17. In retinal whole mounts, retinas of the modified OIR model showed substantial outgrowth of capillaries in the deep layers despite of persistent hyperoxia and similar avascular zones compared with the conventional OIR model. Moreover, neovascular tufts in the modified OIR model were located at the border of avascular zones in the retina, while neovascularizations in the conventional OIR model were predominantly preretinal at the border of avascular zone. The capillaries in the modified OIR model were more regularly formed than those in the conventional OIR model.
Our study showed the outgrowth of the capillary network and intra-retinal neovascularization during persistent hyperoxia in a modified OIR model. The data may indicate a new concept of retinal angiogenesis under VEGF depression. The underlying mechanisms need to be further investigated.
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