The role of growth hormone, insulin-like growth factor and somatostatin in diabetic retinopathy

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are implicated in the aberrant cell growth and pathological neovascularization that characterises proliferative diabetic retinopathy. While serum levels of IGF-I are reported to be either high or low in diabetic patients, there is evidence that local tissue levels of IGF-I may be more relevant to diabetic retinal pathology. IGF-I and IGF binding proteins (IGFBP) are expressed throughout the retina in vascular, neuronal and glial cells, and are altered in response to hyperglycaemia and hypoxia. Further support for a pathological role for local IGF-I comes from studies showing IGF-I to be increased in the vitreal fluids of patients with proliferative diabetic retinopathy. IGF-I may exert its cell growth promoting properties by stimulating a number of pathways including protein-kinase B (Akt), nuclear factor kappa B (NF-kappa B)/AP-1 and hypoxic-inducible factor-1 alpha (HIF-1 alpha). In addition, other growth factors may participate in IGF-I induced cell growth including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF). The importance of the GH/IGF system in diabetic retinopathy and retinal neovascularization has been highlighted by the use of agents that inhibit the system. GH receptor antagonists, GH receptor antisense oligonucleotides, somatostatin analogues and receptor neutralising antibodies to IGF-I reduce hypoxic-induced retinal neovascularization. These approaches may also prove to have benefits for improving vascular patency and vision in patients with diabetic retinopathy.