title: Sildenafil attenuates vaso-obliteration and neovascularization in a mouse model of retinopathy of prematurity.
abstract: OBJECTIVE
  We sought to determine the effect of sildenafil on retinal vascular changes in a mouse model of oxygen-induced retinopathy (OIR).
  
  
  METHODS
  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. Retinal HIF1α protein expression was quantified by Western blotting and normalized to that of β-actin. Right ventricular hypertrophy was measured by Fulton's index as a surrogate for hyperoxia-induced pulmonary hypertension.
  
  
  RESULTS
  At 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. Sildenafil-treated OIR mice had stabilization of retinal HIF1α at P12, immediately after hyperoxia. At P17, sildenafil-treated OIR mice had decreased HIF1α relative to untreated mice. OIR mice developed right ventricle hypertrophy that was significant compared to that in room air controls, which was abrogated by sildenafil.
  
  
  CONCLUSIONS
  Sildenafil treatment significantly decreased retinal vaso-obliteration and neovascularization in a mouse OIR model. These effects are likely due to sildenafil-induced HIF1α stabilization during hyperoxia exposure. Furthermore, we confirm disease overlap by showing that OIR mice also develop hyperoxia-induced right ventricular hypertrophy, which is prevented by sildenafil. 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.
authors: Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Amani A
authors: AA
authors: Fawzi
authors: Jonathan C
authors: JC
authors: Chou
authors: Gina A
authors: GA
authors: Kim
authors: Stuart D
authors: SD
authors: Rollins
authors: Joann M
authors: JM
authors: Taylor
authors: Kathryn N
authors: KN
authors: Farrow
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012178:Retinopathy of Prematurity / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate
keywords: mouse; neovascularization; retinopathy of prematurity; sildenafil; vaso-obliteration