The functional effects and expression of HGF and FGF in the choroid

Purpose Age-related macular degeneration is the most common cause of irreversible visual loss in the increasingly ageing population of the western world. Most current treatments focus on sequestering excess vascular endothelial growth factor (VEGF) produced in response to inflammation and ischaemia. However, compensation by other angiogenic growth factors such as hepatocyte growth factor (HGF) and fibroblast growth factor (FGF) may occur. Methods Expression of HGF and FGF and their receptors MET and FGFR2 was investigated in vivo and in vitro in choroidal endothelial cells (CEC) using immunostaining, western blotting and ELISA. The in vitro response of CEC to these factors was assessed using proliferation and angiogenesis assays. Real time PCR was used to quantify signalling responses through gene expression of key signalling molecules such as HIF and expression of VEGF. Results Expression of HGF, FGF and their receptors was found in human choroid and cultured CEC. Both growth factors increased proliferation and angiogenesis independent of, and additive with VEGF. VEGF and HIF gene expression were altered dependent on growth factor concentration and time. Conclusion Although much research and treatment focuses on VEGF, other growth factors which may compensate for the loss of VEGF signalling have significant stimulatory effects on angiogenesis. This study supports recent clinical advances into combination therapies. Commercial interest