PMID:23093773

Citation	Kurihara, T, Westenskow, PD, Bravo, S, Aguilar, E and Friedlander, M (2012) Targeted deletion of Vegfa in adult mice induces vision loss. J. Clin. Invest. 122:4213-7
Abstract	Current therapies directed at controlling vascular abnormalities in cancers and neovascular eye diseases target VEGF and can slow the progression of these diseases. While the critical role of VEGF in development has been well described, the function of locally synthesized VEGF in the adult eye is incompletely understood. Here, we show that conditionally knocking out Vegfa in adult mouse retinal pigmented epithelial (RPE) cells, which regulate retinal homeostasis, rapidly leads to vision loss and ablation of the choriocapillaris, the major blood supply for the outer retina and photoreceptor cells. This deletion also caused rapid dysfunction of cone photoreceptors, the cells responsible for fine visual acuity and color vision. Furthermore, Vegfa deletion showed significant downregulation of multiple angiogenic genes in both physiological and pathological states, whereas the deletion of the upstream regulatory transcriptional factors HIFs did not affect the physiological expressions of angiogenic genes. These results suggest that endogenous VEGF provides critical trophic support necessary for retinal function. Targeting factors upstream of VEGF, such as HIFs, may be therapeutically advantageous compared with more potent and selective VEGF antagonists, which may have more off-target inhibitory trophic effects.
Links	PubMed PMC3484459 Online version:10.1172/JCI65157
Keywords	Animals; Blindness/genetics; Blindness/metabolism; Blindness/pathology; Eye Proteins/genetics; Eye Proteins/metabolism; Gene Deletion; Mice; Mice, Transgenic; Retinal Cone Photoreceptor Cells/metabolism; Retinal Cone Photoreceptor Cells/pathology; Retinal Pigment Epithelium/metabolism; Retinal Pigment Epithelium/pathology; Vascular Endothelial Growth Factor A/genetics; Vascular Endothelial Growth Factor A/metabolism
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:VEGFA	involved_in	GO:0061304: retinal blood vessel morphogenesis	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.