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Quantification and localization of the IGF/insulin system expression in retinal blood vessels and neurons during oxygen-induced retinopathy in mice

Artikel i vetenskaplig tidskrift
Författare Chatarina Löfqvist
K. L. Willett
Oskar Aspegren
A. C. Smith
C. M. Aderman
K. M. Connor
J. Chen
Ann Hellström
L. E. Smith
Publicerad i Invest Ophthalmol Vis Sci
Volym 50
Nummer/häfte 4
Sidor 1831-1837
ISSN 1552-5783
Publiceringsår 2009
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 1831-1837
Språk en
Länkar dx.doi.org/10.1167/iovs.08-2903
Ämnesord Animals, DNA Primers/chemistry, Disease Models, Animal, Gene Expression Regulation, Humans, Infant, Newborn, Insulin-Like Growth Factor Binding Proteins/*genetics, Insulin-Like Growth Factor I/*genetics, Insulin-Like Growth Factor II/genetics, Mice, Mice, Inbred C57BL, Oxygen/*toxicity, Photoreceptor Cells, Vertebrate/metabolism, RNA, Messenger/metabolism, Receptor, IGF Type 1/*genetics, Receptor, IGF Type 2/genetics, Receptor, Insulin/*genetics, Retinal Neurons/*metabolism, Retinal Vessels/*metabolism, Retinopathy of Prematurity/chemically induced/metabolism, Reverse Transcriptase Polymerase Chain Reaction
Ämneskategorier Medicin och Hälsovetenskap

Sammanfattning

PURPOSE: 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.

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