GENE-EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I, ITS RECEPTOR AND BINDING-PROTEINS IN RETINA UNDER HYPOXIC CONDITIONS

Hypoxia is the main stimulus for neovascularization in the retina. Ins ulin-like growth factor-I (IGF-I) is thought to be one of the mediator s of this process. Severe persistent hypoxia, as occurs in central ret inal artery occlusion, is associated with less retinal neovascularizat ion than relative hypoxia. To study the influence of different types o f hypoxia on the IGF system, we used a model of neonatal rat retina th at responds with neovascularization to a relative hypoxic stimulus pro duced by alternating oxygen concentrations in the respired air. We stu died the influence of 24-hour hypoxia (10% oxygen), 48-hour hyperoxia (75% oxygen), and relative hypoxia (shifting from 48 hours in 75% oxyg en to 24 hours in room air) on the gene expression of IGF-I, IGF-I rec eptor (IGF-IR), and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFB P-3 in retina using a solution hybridization RNase protection assay. H ypoxia induced a significant increase in retinal IGF-IR (178%), IGFBP- 2 (227%), and IGFBP-3 (317%) mRNA; however, retinal IGF-I mRNA was red uced, as well as serum growth hormone (GH). Relative hypoxia caused a similar but less pronounced trend in the gene expression of IGF-IR and the binding proteins, whereas retinal IGF-I mRNA was unchanged and se rum GH was elevated. Both hypoxia and relative hypoxia may cause IGF s ystem stimulation in the retina through upregulation of IGF-IR and IGF BPs. This stimulation may result in neovascularization. However, durin g hypoxia, low levels of tissue oxygenation and reduced local producti on of IGF-I may impede the neovascularization process. Copyright (C) 1 998 by W.B. Saunders Company.