The therapeutic problem of proliferative diabetic retinopathy: Targeting somatostatin receptors

Clinical management of proliferative diabetic retinopathy has changed very little in the last 5 decades, relying primarily on laser ablation of the re tinal vasculature. Several lines of clinical and experimental evidence sugg est that somatostatin analogues may be efficacious in inhibiting neovascula rization associated with proliferative retinopathy but the mechanism of act ion for these compounds is unclear. Inhibition of growth hormone secretion and the subsequent suppression of insulin-like growth factor 1 (IGF-1) prod uction by somatostatin has been suggested as the mechanism of action, howev er, in vitro studies suggest that somatostatin analogues suppress endotheli al cell growth through a direct, somatostatin receptor-mediated inhibition of pro-survival signaling pathways. The advent of a new generation of modif ied peptide and peptidomimetic somatostatin analogues has allowed investiga tors to more carefully define the receptor subtypes responsible for somatos tatin-induced endothelial cell death and may eventually lead to the clinica l development of somatostatin analogues that can reduce endothelial cell pr oliferation, independent of suppression of circulating hormone levels.