Increased expression of KDR/Flk-1 (VEGFR-2) in murine model of ischemia-induced retinal neovascularization

Although the vascular endothelial growth factor (VEGF)/VEGF receptor system plays a critical role in the pathogenesis of ischemic retinal neovascular diseases such as diabetic retinopathy, regulation of VEGF receptor expressi on in ischemic retina has not been fully investigated in vivo. Accordingly, we studied the regulation of Flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2) expre ssion in a mouse model of ischemia-induced retinal neovascularization. Immu nohistochemistry for Flt-1 and KDR/Flk-1 revealed that, in hypoxic retina, the immunoreactivity of KDR/Flk-1 was increased in both intensity and exten t of involvement in the vessels near the avascular area, particularly at th e neovascular tufts, but that the pattern of Flt-1 expression in hypoxic re tina was almost the same as that of control animals. The number of KDR/Flk- 1-positive vessels was significantly increased in hypoxic retina (P < 0.01) . In addition, expression of both Flt-1 and KDR/Flk-l was observed in nonva scular cells of the neural retina. Northern blot analysis demonstrated that the mRNA levels of KDR/Flk-1 were greater in the neovascular retina of hyp oxic animals than in control animals. We suggest that the increased express ion of KDR/Flk-1 in vascular cells might potentiate the VEGF-mediated angio genesis that accompanies many ischemic retinal diseases. (C) 1998 Academic Press.