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Nat Med 1999 Dec;5(12):1390-5
Regulation of vascular endothelial growth factor-dependent retinal
neovascularization by insulin-like growth factor-1 receptor.
Smith LE, Shen W, Perruzzi C, Soker S, Kinose F, Xu X, Robinson G, Driver S, Bischoff
J, Zhang B, Schaeffer JM, Senger DR
Department of Ophthalmology, Harvard Medical School and Children's Hospital, 300 Longwood
Avenue, Boston, Massachusetts 02115, USA. smith_lo@a1.tch.harvard.edu
Although insulin-like growth factor 1 (IGF-1) has been associated with retinopathy, proof of a direct
relationship has been lacking. Here we show that an IGF-1 receptor antagonist suppresses retinal
neovascularization in vivo, and infer that interactions between IGF-1 and the IGF-1 receptor are
necessary for induction of maximal neovascularization by vascular endothelial growth factor
(VEGF). IGF-1 receptor regulation of VEGF action is mediated at least in part through control of
VEGF activation of p44/42 mitogen-activated protein kinase, establishing a hierarchical relationship
between IGF-1 and VEGF receptors. These findings establish an essential role for IGF-1 in
angiogenesis and demonstrate a new target for control of retinopathy. They also explain why
diabetic retinopathy initially increases with the onset of insulin treatment. IGF-1 levels, low in
untreated diabetes, rise with insulin therapy, permitting VEGF-induced retinopathy. |
