The hyperoxic environment associated with mechanical ventilation results in phase 1 ROP. 4, 5 Although oxygen therapy is essential for promoting tissue oxygenation in preterm infants, it has the unfortunate side effect of disrupting the normal transition from in utero hypoxia to normoxia, which is essential for healthy vascular and neuroretinal development in the newborn. 2, 3 Two major predictors of ROP progression in infants are exposure to hyperoxia and gestational age at birth. 1 Despite improvements in therapeutic interventions, ROP continues to be a major cause of childhood visual impairment, with approximately 500 cases of ROP-related blindness reported annually. Retinopathy of prematurity (ROP) is a leading cause of blindness in infants. This study is a first step toward delineating a potential therapeutic role for sildenafil in OIR and further suggests that there may be common pathophysiologic mechanisms underlying hyperoxia-induced retinal and pulmonary vascular disease. Furthermore, we confirm disease overlap by showing that OIR mice also develop hyperoxia-induced right ventricular hypertrophy, which is prevented by sildenafil. These effects are likely due to sildenafil-induced HIF1α stabilization during hyperoxia exposure. Sildenafil treatment significantly decreased retinal vaso-obliteration and neovascularization in a mouse OIR model. OIR mice developed right ventricle hypertrophy that was significant compared to that in room air controls, which was abrogated by sildenafil. At P17, sildenafil-treated OIR mice had decreased HIF1α relative to untreated mice. Sildenafil-treated OIR mice had stabilization of retinal HIF1α at P12, immediately after hyperoxia. Right ventricular hypertrophy was measured by Fulton's index as a surrogate for hyperoxia-induced pulmonary hypertension.Īt P12, OIR mice treated with sildenafil demonstrated a 24% reduction in vaso-obliteration ( P < 0.05), whereas at P17, treated animals showed a 50% reduction in neovascularization ( P < 0.05) compared to dextrose-treated controls. ![]() Retinal HIF1α protein expression was quantified by Western blotting and normalized to that of β-actin. Vascular defects in OIR mice were quantified by measuring vaso-obliteration at postnatal days 12 and 17 (P12 and P17) and neovascularization at P17 to compare sildenafil-treated to dextrose-treated OIR mice. We sought to determine the effect of sildenafil on retinal vascular changes in a mouse model of oxygen-induced retinopathy (OIR).
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