title: Temporal requirement of RPE-derived VEGF in the development of choroidal vasculature.
abstract: Vascular endothelial growth factor (VEGF-A or VEGF) is a potent growth factor for the development of retinal and choroidal vasculatures. To define the temporal requirement of the retinal pigmented epithelium (RPE)-derived VEGF in choroidal vascular development, we generated conditional VEGF knockout mice using an inducible Cre/lox system. The loss of the RPE-derived VEGF was confirmed with immunoblotting and immunohistochemistry. Retinal function and structure were assessed with electroretinography and histology, respectively. Choroidal vascular density was analyzed with computer-assisted semi-quantitative assay using fluorescently labeled choroidal flat-mounts. Induction of RPE-specific VEGF disruption at embryonic day 10 (E10) or E13 for 2 days caused regulatable decreases in choroidal vascular density, photoreceptor function, and photoreceptor outer nuclear layer thickness. The loss of the RPE-produced VEGF after E15 did not cause detectable defects in choroidal vasculatures and photoreceptor function and morphology. These results suggest that the RPE-derived VEGF plays a critical role in choroidal vascular development during organogenesis before E15.
authors.affiliation: Department of Medicine Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Yun-Zheng
authors.initials: YZ
authors.lastname: Le
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Bai
authors.forename: Meili
authors.initials: M
authors.lastname: Zhu
authors.forename: Lixin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002829:Choroid / Q000166:cytology* / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D004596:Electroretinography / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D007091:Image Processing, Computer-Assisted / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012160:Retina / Q000502:physiology / Q000648:ultrastructure; D012171:Retinal Vessels / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000172:deficiency / Q000378:metabolism*
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D004318:Doxycycline