title: Comparative effects of early postnatal ibuprofen and indomethacin on VEGF, IGF-I, and GH during rat ocular development.
abstract: OBJECTIVE
  Ibuprofen and indomethacin are nonselective prostaglandin synthetase inhibitors that have been shown to improve oxygen-induced retinopathy in mice. Vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-I, and growth hormone (GH) are potent growth factors involved in retinal development. This study was conducted to examine and compare the effects of early postnatal ibuprofen and indomethacin on ocular and systemic VEGF, IGF-I, and GH during rat ocular development.
  
  
  METHODS
  Newborn rats were treated with intraperitoneal injections of low and high doses of ibuprofen or indomethacin at birth (postnatal day [P]1) and on P2 and P3. A control group received equivalent volumes of saline. At P14, vitreous fluid, retinal homogenates, and serum were analyzed for VEGF, IGF-I, and GH protein levels. Retinal mRNA expression of VEGF splice variants (VEGF188, VEGF164, VEGF120), VEGF receptors (VEGFR-1, VEGFR-2, Npn-1, Npn-2), and pigment epithelium-derived factor (PEDF) were also examined.
  
  
  RESULTS
  Animals treated with high-dose ibuprofen had significantly lower somatic growth and higher serum and vitreous IGF-I levels. High-dose ibuprofen decreased retinal VEGF levels and retinal VEGF164, VEGF120, and VEGFR-2 transcripts, resulting in a significant increase in the cecal period in 87% of rats at P14. Both indomethacin doses suppressed retinal VEGF164 transcripts without affecting VEGF receptors.
  
  
  CONCLUSIONS
  Ibuprofen may be more effective than indomethacin for suppression of retinal VEGF signaling, suggesting a possible therapy for retinal neovascularization. However, deficits in somatic growth concurrent with higher systemic IGF-I levels suggests decreased IGF-I bioactivity. These adverse effects should be considered.
authors.affiliation: Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of California Irvine, Irvine, and Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Miller Children's Hospital, Long Beach, California, USA.
authors.forename: Kay D A
authors.initials: KD
authors.lastname: Beharry
authors.forename: Houchang D
authors.initials: HD
authors.lastname: Modanlou
authors.forename: Jamal
authors.initials: J
authors.lastname: Hasan
authors.forename: Zahra
authors.initials: Z
authors.lastname: Gharraee
authors.forename: Patricia
authors.initials: P
authors.lastname: Abad-Santos
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Sills
authors.forename: Amanda
authors.initials: A
authors.lastname: Jan
authors.forename: Stephen
authors.initials: S
authors.lastname: Nageotte
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Aranda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005123:Eye / Q000254:growth & development*; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014822:Vitreous Body / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D040262:Receptors, Vascular Endothelial Growth Factor; D007052:Ibuprofen; D007213:Indomethacin