title: Quantification and localization of the IGF/insulin system expression in retinal blood vessels and neurons during oxygen-induced retinopathy in mice.
abstract: OBJECTIVE
  Retinopathy is a result of pathologic angiogenesis influenced by insulinlike growth factor (IGF)-1. The authors examined the local expression of the IGF/insulin family.
  
  
  METHODS
  In retinas with and without oxygen-induced retinopathy, the authors assessed with real-time RT-PCR mRNA expression of the IGF-1 receptor (IGF-1R), insulin receptor (IR), IGF-1, IGF-2, insulin (Ins2), and IGF-binding protein 1 (IGFBP1) to IGFBP6 in total retina from postnatal day (P) 7 to P33 to examine changes over time with the induction of retinopathy and at P17 on laser-captured retinal components to quantitatively localize mRNA expression in the ganglion cell layer, the outer nuclear layer, the inner nuclear layer, normal blood vessels, and neovascular tufts.
  
  
  RESULTS
  IGF-1R and IR are expressed predominantly in photoreceptors and in vessels, with scant expression in the rest of the neural retina. IGF-1R expression is more than 100-fold greater than IR. The major local growth factor (expressed in photoreceptors and in blood vessels) is IGF-2 (approximately 1000-fold greater than IGF-1). IGF-1 (approximately 600 copies/10(6) cyclophilin) is expressed throughout the retina. IGFBP2, IGFBP4, and IGFBP5 expression is unchanged with increasing retinal development and with the induction of retinopathy. In contrast, IGFBP3 expression increased more than 5-fold with hypoxia, found in neovascular tufts.
  
  
  CONCLUSIONS
  IGF-1R, IR, and the ligand IGF-2 are expressed almost exclusively in photoreceptors and blood vessels. IGFBP3 and IGFBP5 expression increases in neovascular tufts compared with normal vessels. IGF-1 is expressed throughout the retina at much lower levels. These results suggest cross-talk between vessels and photoreceptors in the development of retinopathy and retinal vasculature.
authors.affiliation: Department of Ophthalmology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Chatarina
authors.initials: C
authors.lastname: Lofqvist
authors.forename: Keirnan L
authors.initials: KL
authors.lastname: Willett
authors.forename: Oskar
authors.initials: O
authors.lastname: Aspegren
authors.forename: Alexandra C H
authors.initials: AC
authors.lastname: Smith
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Aderman
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Ann
authors.initials: A
authors.lastname: Hellstrom
authors.forename: Lois E H
authors.initials: LE
authors.lastname: Smith
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity*; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D017527:Receptor, IGF Type 2 / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics*; D055351:Retinal Neurons / Q000378:metabolism*; D012171:Retinal Vessels / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000139:chemically induced / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D010100:Oxygen