RGD Reference Report - Targeted deletion of Vegfa in adult mice induces vision loss. - Rat Genome Database

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Targeted deletion of Vegfa in adult mice induces vision loss.

Authors: Kurihara, T  Westenskow, PD  Bravo, S  Aguilar, E  Friedlander, M 
Citation: Kurihara T, etal., J Clin Invest. 2012 Nov;122(11):4213-7. doi: 10.1172/JCI65157. Epub 2012 Oct 24.
RGD ID: 11075234
Pubmed: PMID:23093773   (View Abstract at PubMed)
PMCID: PMC3484459   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI65157   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
blindness  ISOVegfa (Mus musculus)11075234; 11075234 RGD 
blindness  IMP 11075234 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Vegfa  (vascular endothelial growth factor A)

Genes (Mus musculus)
Vegfa  (vascular endothelial growth factor A)

Genes (Homo sapiens)
VEGFA  (vascular endothelial growth factor A)


Additional Information