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

• 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.

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)