Acute lung injury correlates with retinal vascular injury in an in vivo model of retinopathy of prematurity

Background: The retina and lung blood vessels develop in a hypoxic in utero environment. Oxygen exposure in premature infants has been separately implicated in the development of Chronic Lung Disease (CLD) and Retinopathy of Prematurity (ROP). However, a direct link between CLD and ROP has not been established. Methods: Using a neonatal mouse model of oxygen-induced retinopathy (OIR), newborn C57BL6/J mice pups (n =9) were exposed to 77% hyperoxia from postnatal day 7 (P7) to P12 before placing in room air. From P17 to P19, in vivo retinal imaging was performed with fluorescein angiography followed by ex vivo retinal histology and lung histology. Bronco-alveolar lavage (BAL) was also done for cell count and protein estimation. Results: Fluorescein angiography (FA) following hyperoxia exposure showed distinct areas of capillary non-perfusion and increased dilation and tortuosity of retinal vessels, while the room air raised mice showed uniform vascularization. Retinal histology reveals vascular engorgement and retinal neovascular nuclei above the inner limiting membrane. Lung histology in OIR mice had cellular infiltration and thickening of the alveolar septa, vascular congestion and loss of regular alveolar architecture when compared to controls. There was 3 fold increase in protein count and 4 fold increase in total inflammatory cells in the BAL fluid of OIR mice (p<0.01). Conclusions: Hyperoxia exposure results in both lung and retinal injury and inflammation. Study of inflammatory pathways propagating this injury, may lead to therapeutic options to prevent morbidity and mortality in chronic lung disease as well as blindness from ROP.