A role for hepatocyte growth factor in diabetic retinopathy?

Since Michaelson’s original hypothesis in 19481that a diffusible biochemical agent was involved in diabetic retinopathy an extensive list of potential angiogenic factors has been generated.2 Of these, insulin-like growth factor, transforming growth factor β, fibroblast growth factor, members of the interleukin family, and vascular endothelial growth factor (VEGF) are prominent in the neovascularisation associated with proliferative diabetic retinopathy (PDR). The most extensively studied of these is VEGF, which increases vascular permeability and is a potent stimulator of angiogenesis.3 4 The ability to inhibit VEGF action both in vitro and in vivo by applying blocking antibodies, antisense oligonucleotides, or soluble receptor has heralded modulation of VEGF as the way forward in treating PDR. However, there is considerable evidence that VEGF levels are low or even absent in some patients with active PDR and that VEGF alone is insufficient to promote PDR in animal models.5 6 Tolentino and colleagues demonstrated that repeated intravitreal injections of VEGF, while being sufficient to …