The aim of the present study was to investigate the potential mechanism of
retinopathy of prematurity (ROP) using an
oxygen-induced retinopathy (OIR) mouse model. For experiments, mice were divided into either the OIR group or control group.
Fluorescein isothiocyanate-dextran cardiac perfusion and stretched retina preparation were performed. The total retina area, area of instillation, density of microvascular network, area of new blood vessels, vein width and the tortuosity of arteries were measured. Next, mice were randomly assigned into the PBS, soluble
TEK receptor tyrosine kinase (sTie2)-fusion
protein (Fc),
angiopoietin 1 (Ang1),
ranibizumab,
ranibizumab + sTie2-Fc and
ranibizumab + Ang1 treatment groups. Following housing for 5 days, the
body weight of each mouse was recorded. Mice in the OIR group presented smaller total retina area and larger area of instillation, larger area of new blood vessels, and higher microvascular network density compared with the control PBS group. Obvious retinal vein dilatation and arterial tortuosity were identified in the OIR group. The amount of endotheliocyte nuclei of new vessels beyond the inner limiting membrane was larger in the OIR group compared with the control group. Furthermore in the next set of experiments, a larger area of instillation, smaller area of new blood vessels and decreased amount of endotheliocyte nuclei of new vessels were observed in the sTie2-Fc group, Ang1 group,
ranibizumab group,
ranibizumab + sTie2-Fc group and
ranibizumab + Ang1 group compared with the PBS group. Specifically, the
ranibizumab + sTie2-Fc group and
ranibizumab + Ang1 group demonstrated markedly reduced retina instillation area and microvascular network density in the instillation area. Total retina area and
body weight following 10 days of the experiment for the
ranibizumab group were significantly lower compared with other groups. In conclusion, the combined regulation of the Ang/Tie2 and the
vascular endothelial growth factor (
VEGF)/
VEGF receptor pathways markedly increased the efficacy of treatment with
retinal neovascularization (RNV). Regulation of these pathways has a potential for treating RNV, in particular ROP.