Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) co-exist in 30% of premature neonates with extremely low birth weight and contribute to high morbidity. Infants with significant BPD are at high risk for BPD-associated pulmonary hypertension (PH) and right-sided heart failure. Current therapeutic approaches address each condition separately, without considering a possible shared vascular mechanism. In this proposal, we will dissect the role of cGMP in the vascular pathogenesis of ROP and BPD. We will use the mouse oxygen-induced retinopathy (OIR) model. We hypothesize that PDE5 inhibitors, which elevate cGMP levels, given during high oxygen will have a beneficial role by promoting normal retinal and lung vascular development, while simultaneously preventing BPD-associated PH and right heart failure. The proposed study will identify a safe and effective therapeutic window for the use of PDE5 inhibitors in neonatal mice and enhance understanding of the role of cGMP in retinal vascular development. Success of the current proposal will allow further studies in larger animal models, as a pre-requisite for human clinical trials. PDE5 inhibitors are readily available and are being used in term infants with PH, where the pharmacokinetics have been validated and the drug shown to be safe.
|Effective start/end date||9/1/13 → 7/31/14|
- Northwestern Memorial Hospital (Exhibit B.7)