| First Author | Foxton RH | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 4 | Pages | 1379-90 |
| PubMed ID | 23416159 | Mgi Jnum | J:195315 |
| Mgi Id | MGI:5477885 | Doi | 10.1016/j.ajpath.2012.12.032 |
| Citation | Foxton RH, et al. (2013) VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. Am J Pathol 182(4):1379-90 |
| abstractText | 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. |
