UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma

Foxton, RH; Finkelstein, A; Vijay, S; Dahlmann-Noor, A; Khaw, PT; Morgan, JE; Shima, DT; (2013) VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. American Journal of Pathology , 182 (4) 1379 - 1390. 10.1016/j.ajpath.2012.12.032. Green open access

[thumbnail of Foxton_AJP_Author_Accepted_Manuscript.pdf]
Preview
PDF
Foxton_AJP_Author_Accepted_Manuscript.pdf
Available under License : See the attached licence file.

Download (777kB)

Abstract

Vascular endothelial growth factor A (VEGF-A) is a validated therapeutic target in several angiogenic- and vascular permeability-related pathological conditions, including certain cancers and potentially blinding diseases, such as age-related macular degeneration and diabetic retinopathy. We and others have shown that VEGF-A also plays an important role in neuronal development and neuroprotection, including in the neural retina. Antagonism of VEGF-A function might therefore present a risk to neuronal survival as a significant adverse effect. Herein, we demonstrate that VEGF-A acts directly on retinal ganglion cells (RGCs) to promote survival. VEGF receptor-2 signaling via the phosphoinositide-3-kinase/Akt pathway was required for the survival response in isolated RGCs. These results were confirmed in animal models of staurosporine-induced RGC death and experimental hypertensive glaucoma. Importantly, we observed that VEGF-A blockade significantly exacerbated neuronal cell death in the hypertensive glaucoma model. Our findings highlight the need to better define the risks associated with use of VEGF-A antagonists in the ocular setting.

Type: Article
Title: VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ajpath.2012.12.032
Language: English
Additional information: © 2013 American Society for Investigative Pathology. Published by Elsevier.
Keywords: Animals, Apoptosis, Caspases, Cell Death, Cells, Cultured, Cytoprotection, Disease Models, Animal, Glaucoma, Neuropilins, Neuroprotective Agents, Neutralization Tests, Ocular Hypertension, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Rats, Rats, Sprague-Dawley, Retina, Retinal Ganglion Cells, Signal Transduction, Toxicity Tests, Acute, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-2
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1386403
Downloads since deposit
222Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item