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Abstract #52614 Published in IGR 15-1

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; Ng YS
American Journal of Pathology 2013; 182: 1379-1390


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.

National Institute for Health Research, Biomedical Research Centre Moorfields Eye Hospital.

Full article

Classification:

11.8 Neuroprotection (Part of: 11 Medical treatment)
11.15 Other drugs in relation to glaucoma (Part of: 11 Medical treatment)



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