Retinal Expression of IGF Binding Proteins

Abstract

Purpose: : Insulin-like growth factor I (IGF-I) has proven to be essential in preventing retinopathy of prematurity (ROP) by permitting normal retinal vascular growth in the first phase of ROP. Insulin-like growth factor binding protein-3 (IGFBP-3) has been shown to act independently of IGF-I in preventing oxygen-induced vessel loss and in promoting normal vascular regrowth after vascular destruction in the retina. Different IGF binding proteins are known, here we investigate six binding proteins and their expression profiles in the ischemic retina following oxygen-induced vessel loss.

Methods: : C57Bl/6 mice were put in 75% oxygen between postnatal day 7 (P7) and P12 in order to induce vessel loss. Retinas become hypoxic after return to room air at P12 following the hyperoxia-induced vaso-obliteration. The retinas were then collected at P8, P12, P15 and P17 and RNA was isolated for cDNA preparation. Real time RT PCR was used to quantify the gene expression for each binding protein at the different time points. Mice isolated in normoxia only were controls.

Results: : A marked induction (>7 fold) of IGFBP-3 mRNA expression during the hypoxic phase of retinopathy (P12-P17) was observed compared to normoxic controls. Also, the IGFBP-1 and IGFBP-6 mRNA expression levels were markedly elevated during this phase (>20 fold and 7 fold, respectively), compared to normoxic levels. The mRNA expression of IGFBP-2 and -5 was only moderately elevated with hypoxia (<1.25 fold) compared to normoxic controls. IGFBP-4 mRNA production was stable during oxygen induced retinopathy.

Conclusions: : The relative amounts of mRNA expression suggest that IGFBP-1, -3 and -6 do play an important role in the modulation of retinopathy in the oxygen-induced retinopathy model.

Keywords: growth factors/growth factor receptors • neovascularization • hypoxia