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 expression 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) expression in a mouse model of ischemia-induced retinal neovascularization. Immunohistochemistry for Flt-1 and KDR/Flk-1 revealed that, in hypoxic retina, the immunoreactivity of KDR/Flk-1 was increased in both intensity and extent of involvement in the vessels near the avascular area, particularly at the neovascular tufts, but that the pattern of Flt-1 expression in hypoxic retina 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-1 was observed in nonvascular cells of the neural retina. Northern blot analysis demonstrated that the mRNA levels of KDR/Flk-1 were greater in the neovascular retina of hypoxic animals than in control animals. We suggest that the increased expression of KDR/Flk-1 in vascular cells might potentiate the VEGF-mediated angiogenesis that accompanies many ischemic retinal diseases.