Foxton, RH; Finkelstein, A; Vijay, S; Dahlmann-Noor, A; Khaw, PT; Morgan, JE; Shima, DT; Foxton, RH; Finkelstein, A; Vijay, S; Dahlmann-Noor, A; Khaw, PT; Morgan, JE; Shima, DT; Ng, YS; - view fewer (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.

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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.

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