The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Targeted deletion of Vegfa in adult mice induces vision loss
Open accessAbstract
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.
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Cites
Ranibizumab for Neovascular Age-Related Macular Degeneration
Rosenfeld, P. J., Brown, D. M., Heier, J. S., Boyer, D. S., Kaiser, P. K., Chung, C. Y., & Kim, R. Y. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054481 · Cited by 5,886
Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
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VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia
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Ranibizumab and bevacizumab for neovascular age-related macular degeneration
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Pegaptanib for neovascular age-related macular degeneration
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Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo
Jin, K., Zhu, Y., Sun, Y., Mao, X. O., Xie, L., & Greenberg, D. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.182296499 · Cited by 1,507
HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α
Arany, Z., Foo, S.-Y., Ma, Y., Ruas, J. L., Bommi-Reddy, A., Girnun, G., Cooper, M., Laznik, D., Chinsomboon, J., Rangwala, S. M., et al. (2008) · Nature · doi:10.1038/nature06613 · Cited by 1,054
Age-related macular degeneration
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Self-citationInducible Expression of Cre Recombinase in the Retinal Pigmented Epithelium
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The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422
Pathophysiology of diabetic retinopathy: The old and the new
Kusuhara, S., Fukushima, Y., Ogura, S., Inoue, N., & Uemura, A. (2018) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2018.0182 · Cited by 250
VEGF regulates local inhibitory complement proteins in the eye and kidney
Keir, L. S., Firth, R., Aponik, L., Feitelberg, D., Sakimoto, S., Aguilar, E., Welsh, G. I., Richards, A., Usui, Y., Satchell, S. C., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86418 · Cited by 154
Self-citationPeden, M. C., Suñer, I. J., Hammer, M. E., & Grizzard, W. S. (2015) · Ophthalmology · doi:10.1016/j.ophtha.2014.11.018 · Cited by 131
Metadata
- Authors
- Kurihara, T., Westenskow, P. D., Bravo, S., Aguilar, E., & Friedlander, M.
- Venue
- Journal of Clinical Investigation
- Published
- 2012-10-24
- Volume
- 122
- Issue
- 11
- Pages
- 4213-4217
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1985388968
- Cited by
- 328
- References
- 10
- FWCI
- 22.70
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kurihara, T., Westenskow, P. D., Bravo, S., Aguilar, E., & Friedlander, M. (2012). Targeted deletion of Vegfa in adult mice induces vision loss. Journal of Clinical Investigation. https://doi.org/10.1172/jci65157
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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