Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization

Purpose. Vascular endothelial growth factor (VEGF) is an angiogenic peptide that has been suggested to be important in the pathogenesis of choroidal n eovascularization. We investigated the transcription of VEGF; and its recep tor KDR/flk-1 genes during the development of experimentally induced choroi dal neovascularization. Methods. Rat VEGF or KDR cDNA was inserted in PGEM or pBluescript to prepar e antisense or sense riboprobes. Multiple krypton laser burns were applied to the posterior pole of pigmented rat eyes according to a previously descr ibed protocol which produces choroidal neovascularization. At intervals of up to 4 weeks after photocoagulation, the eyes were removed and cut into th in sections. The sections were subjected to in situ hybridization with digo xigenin (DIG)-labeled single-strand rat VEGF and KDR cDNA riboprobes. Results. In normal adult rat retinas, VEGF and KDR mRNA expression was main ly observed in the ganglion cell and the inner nuclear layers. During the d evelopment of neovascularization, VEGF and KDR mRNAs were detected in retin al pigment epithelial-like cells, fibroblast-like cells and endothelial cel ls in neovascular lesions. The level of expression was strongest at 1 week after photocoagulation in lasered lesions, and decreased by 4 weeks after p hotocoagulation. Conclusions. Our findings demonstrate that expression of VEGF and its recep tor KDR may play a role in the formation of experimentally induced choroida l neovascularization. In this study, VEGF and its receptor were co-localize d, suggesting that an autocrine and/or paracrine mechanism may be operative .