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

Abstract

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 photo-receptors 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/106 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 crosstalk between vessels and photoreceptors in the development of retinopathy and retinal vasculature. © Association for Research in Vision and Ophthalmology.