IGF-1 and Retinopathy of Prematurity in the Preterm Infant

BACKGROUND: Retinopathy of prematurity (ROP) continues to be a major cause of blindness in children. Although ablation of the retina reduces the incidence of blindness by suppressing the neovascular phase of ROP, the visual outcomes after treatment are often poor. Preventive therapy is required and will likely come from a better understanding of the pathophysiology of the disease. OBJECTIVES: To study the role of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) in both the proliferative phase of ROP (phase II) and in the early phase when blood vessels are lost. METHODS: Using both a mouse model of ROP and clinical studies the relationship between IGF-1, VEGF and both vessel loss and vessels proliferation in the retina was studied. RESULTS: IGF-1 is required for maximum VEGF activation of vascular endothelial cell proliferation and survival pathways. IGF-1 levels are deficient after premature birth, setting the stage for retinal vascular loss and ROP. CONCLUSIONS: Restoration of IGF-1 to levels found in utero may help prevent ROP.