Abstract
Bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) are two severe disorders which arise in the lungs and eyes of preterm infants exposed to prolonged supplemental oxygen. Due to the lack of a clinically relevant animal model of simultaneous lung and eye disease, the shared molecular pathways underlying the development of these two disorders remain unexplored. To address this, we assessed the development of lung disease in a supplemental oxygen model widely used to assess ROP. Neonatal C57Bl/6 mice were exposed to supplemental oxygen (75% oxygen) for 5 days from postnatal day (PN) 7 until PN12, returned to room air and assessed at either PN12, PN18, PN40 and PN80 alongside room air controls. Histopathology of the lung and retina were used to determine disease severity and progression. The coincident model revealed BPD-like mild alveolar wall thickening in the lungs of mice exposed to supplemental oxygen at PN12 and PN18, alongside ROP-like inner vascular degeneration in the retina. At PN40 and PN80, severe airspace enlargement and simplification were observed in lungs of mice in the oxygen group, with concurrent thinning of the choroid layer in the eye, successfully reproducing the key features of human BPD and ROP. Immune cell infiltration was also elevated in the airspaces of supplemental oxygen exposed mice at each of the assessed timepoints. This new model of coincident BPD and ROP provides an opportunity to evaluate the mechanisms connecting these two disorders, where similar pathways found in both BPD and ROP could aid in the development of a single therapy to ameliorate damage to both tissues in preterm infants.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, OA274.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019