title: Regulation of fibroblast growth factor 2 expression in oxygen-induced retinopathy.
abstract: OBJECTIVE
  Fibroblast growth factor (FGF) 2 is a potent endothelial cell mitogen and survival factor that is postulated to participate in the pathogenesis of retinopathy of prematurity (ROP). The purpose of the current study was to determine the transcriptional and translational regulation of FGF2 expression in oxygen-induced retinopathy (OIR), the animal model of ROP.
  
  
  METHODS
  We examined FGF2 protein and mRNA expression and optokinetic visual responses in transgenic mice possessing a dual-luciferase bicistronic transgene containing a 5'-internal ribosome entry site (IRES) of FGF2.
  
  
  RESULTS
  We found that retinal FGF2 protein isoform expression varies with age but not in response to OIR. Analysis of luciferase, protein, and mRNA data indicate that FGF2 protein expression is translationally repressed during the vaso-obliterative phase of OIR, possibly by inhibiting elongation. At the transition from vaso-obliteration to neovascularization, heightened FGF2 protein expression corresponds to maintenance of IRES activity and diminished cap-dependent translational activity. During neovascularization, FGF2 expression is primarily regulated by transcription. Mice recovering from OIR display alterations in visual optokinetic responses and increased FGF2 protein expression at 6 weeks of age.
  
  
  CONCLUSIONS
  In total, these findings illustrate the complexity of translational and transcriptional regulation of FGF2 protein expression in OIR. The augmentation of FGF2 expression and reduced optokinetic responses during the resolution of surface vasculopathy may indicate a role for FGF2 in the maintenance of neuroretinal function in OIR/ROP.
authors.affiliation: Department of Pediatrics, Penn State Hershey Eye Center, Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States.
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Ophthalmology, Penn State Hershey Eye Center, Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States.
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Barber
authors.affiliation: Department of Pediatrics, Penn State Hershey Eye Center, Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States Department of Pediatrics, Baystate Medical Center, Springfield, Massachusetts, United States.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Shenberger
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D010100:Oxygen
keywords: fibroblast growth factor 2; internal ribosome entry site; oxygen; retina; retinopathy of prematurity