VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma.
| Autor: | Foxton RH; National Institute for Health Research, Biomedical Research Centre Moorfields Eye Hospital., Finkelstein A, Vijay S, Dahlmann-Noor A, Khaw PT, Morgan JE, Shima DT, Ng YS |
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| Jazyk: | angličtina |
| Zdroj: | The American journal of pathology [Am J Pathol] 2013 Apr; Vol. 182 (4), pp. 1379-90. Date of Electronic Publication: 2013 Feb 12. |
| DOI: | 10.1016/j.ajpath.2012.12.032 |
| Abstrakt: | 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. (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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