Abstract
Abstract: :
Purpose: Gene targeted mice expressing the single VEGF 188 isoform were reported to have impaired retinal vessel development and a persistent hyaloid artery. In this study we analyzed the impact of this developmental anomaly in the adult retina. Methods: Retinal vessels of VEGF 188 transgenic mice (8 weeks postnatal) were visualized by intracardial perfusion with FITC conjugated Concanavalin A. The number of arteries and veins per retina as well as the capillary length were measured with IP-Lab software. Vascular endothelial cells and smooth muscle cells/pericytes were visualized by immunohistochemistry for CD31 (PECAM-1) and smooth muscle actin, respectively. Hematoxylin and eosin staining of paraffin embedded sections was used to examine retinal morphology and the hyaloid vessels. Results: Perfusion of retinal vessels revealed that the retina was vascularized to the periphery. In the VEGF188 homozygous (188/188) animals an increased number of arteries and veins as well as anastomosing vessels were detected. In wildtype, in VEGF 188/+ heterozygous and in VEGF 188/188 homozygous mice three retinal capillary layers could be distinguished. The second and third layer of the vessels in VEGF 188/188 animals, however, was less dense. Sections of the VEGF188 homozygous mouse retinas revealed that the hyaloid artery penetrated the retinal surface inducing a retinal fold with consecutive atrophy of the photoreceptors and the inner nuclear layer. Conclusions: Mice that express only VEGF 188 showed diminished perfusion of the retinal inner nuclear layer. Tractional retinal folds were observed in the areas where persistent hyaloid vessels revascularized the retina. Atrophy of the photoreceptors and inner nuclear layer was observed in those areas. These results suggest that the VEGF 188 isoform alone is not sufficient for normal retinal development and that expression of the smaller VEGF 164 and 120 isoforms is necessary for the development of normal retinal architecture.
Keywords: growth factors/growth factor receptors • retina • animal model