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Updated: May 14, 2026
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma
Richard H Foxton1, Arthur Finkelstein, Sauparnika Vijay
1National Institute for Health Research, Biomedical Research Centre Moorfields Eye Hospital.
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.
Insights
Vascular endothelial growth factor A (VEGF-A) is vital for retinal ganglion cell (RGC) survival. Blocking VEGF-A worsens RGC death in glaucoma models, indicating potential risks of anti-VEGF therapies.
Area of Science:
- Ophthalmology
- Neuroscience
- Molecular Biology
Background:
- Vascular endothelial growth factor A (VEGF-A) is a key target for anti-angiogenic therapies in cancer and blinding diseases.
- VEGF-A also plays a critical role in neuronal development and neuroprotection within the neural retina.
- Antagonism of VEGF-A may pose a risk to neuronal survival, particularly in ocular conditions.
Purpose of the Study:
- To investigate the direct role of VEGF-A in the survival of retinal ganglion cells (RGCs).
- To elucidate the signaling pathways involved in VEGF-A-mediated RGC survival.
- To assess the impact of VEGF-A blockade on RGC survival in disease models.
Main Methods:
- Isolated RGCs were used to study VEGF-A's direct effects on survival.
- VEGF receptor-2 and phosphoinositide-3-kinase/Akt signaling pathways were investigated.
- Animal models, including staurosporine-induced RGC death and experimental hypertensive glaucoma, were employed.
Main Results:
- VEGF-A directly promotes the survival of RGCs.
- VEGF receptor-2 signaling through the PI3K/Akt pathway is essential for this survival.
- VEGF-A blockade significantly increased RGC death in a hypertensive glaucoma model.
Conclusions:
- VEGF-A is a crucial neuroprotective factor for RGCs.
- The findings underscore the potential adverse effects of VEGF-A antagonists on RGC survival.
- Further research is needed to balance the benefits and risks of VEGF-A inhibition in ocular treatments.
