The 50/10 Oxygen-Induced Retinopathy Model Serves as a Hyperoxia and Hypoxia Model of Bronchopulmonary Dysplasia

Abstract

BackgroundAnimal models of bronchopulmonary dysplasia (BPD) are mainly created by hyperoxia exposure. However, these models do not fully recapitulate BPD pathophysiology as observed in clinical practice. To find a better BPD model, we established a rat 50/10 oxygen-induced retinopathy (OIR) model and analyzed the pathologic features of the lungs. MethodsThe rat OIR model was established by exposing newborn rats (P0) to 50% and 10% oxygen (hyperoxia and hypoxia) on alternating days for 14 days. Lungs were harvested immediately on postnatal day 14 (P14) and on P18 after 4 days of normoxia exposure for hematoxylin and eosin staining, antialpha smooth muscle actin (α-SMA) immunohistochemistry and Picrosirius red staining of collagen. Retinas were obtained to confirm successful model establishment by isolectin B4 staining of retinal vasculature. ResultsOIR rats presented with fewer and enlarged alveoli, and the septal walls were thicker than those in age-matched controls. α-SMA immunohistochemistry indicated increased abundance of myofibroblasts in OIR rats. At P18, α-SMA-positive myofibroblasts were present at extremely low levels from the alveolar walls of control rats, while OIR rats showed myofibroblast persistence. The amount of collagen in OIR rats was also higher than that in control rats at both P14 and P18 as evidenced by Picrosirius red staining. ConclusionsAlveolar changes observed by hematoxylin and eosin staining, prolonged and stronger α-SMA expression and augmented collagen accumulation resemble the histopathology of BPD, suggesting that the rat 50/10 OIR model is suitable for use in BPD research.