Preliminary study of retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice

摘要

Background: The main risk factors of retinopathy of prematurity (ROP) are low gestational age and low birth weight, which are mainly caused by preterm birth. Currently, the animal model of oxygen-induced retinopathy (OIR) in mice is the most widely used model in ROP-associated studies. However, the experimental mice are normal-term pups, and may not mimic the pathogenic status of human ROP patients. In this study, we investigated the retinal pathological features in preterm birth pups exposed to an animal model of oxygen-induced retinopathy in mice. Methods: Preterm-birth mice were obtained from pregnant C57BL/6J mice that were induced by an intraperitoneal injection of lipopolysaccharide (LPS). The preterm and control mice were treated with high oxygen (75 %) from postnatal day 7 (P7) to P12. The mice were perfused with high-molecular-weight FITC-dextran on P12, P15 and P17, and the retinas were whole-mounted and imaged. Vascular endothelial growth factor (VEGF) mRNA was also detected. Cross-sections of the retina were stained with hematoxylin and eosin (H&E) to identify preretinal neovascular tufts. For general observation, whole retinal images were also obtained using a microscope. Results: Leakage of the retinal blood vessels was aggravated in the preterm mice, particularly on P12 and P15. The non-perfused areas of the retina (pixel value, 183,673 ± 28,148 vs 132,110 ± 23,732, P = 0.009) and the number of preretinal endothelial cell nuclei were smaller (30.17 ± 8.33 vs 22.17 ± 6.74, P < 0.0001) on P17. The VEGF mRNA levels in the retinas were higher on P12 and P15 but lower on P17, compared with the control mice. Retinal hemorrhage was observed in the preterm mouse group (five out of six examined eyes). Conclusions: Preterm-birth mice that were subject to OIR exhibited several pathological features, such as retinal hemorrhage, severe retinal leakage and moderate retinal neovascularization, which were similar to the clinical manifestations in ROP patients.