In a new study published in Signal Transduction and Targeted Therapy, researchers at UVA Health have identified a new cause of excessive blood vessel growth in the eye, opening up potential avenues for research into treatments for angiogenic eye diseases.
Give me some background.
Vascular endothelial growth factor-A (VEGF-A) is a known regulator of blood vessel growth and the most common target of inhibitors approved for angiogenic diseases that cause vision loss. However, anti-VEGF therapies are also known for their initial dramatic efficacy and longer-term diminishment.
Tell me about the study.
Researchers induced choroidal neovascularization in mice and tracked mRNA levels over time. They then inhibited fat mass and obesity-associated protein (FTO), a demethylase, that was unexpectedly found to significantly impact the regulation of ocular neovascularization via an epigenetic mechanism.
So what did they find?
Inhibiting FTO resulted in reduced neovascularization and suppressed VEGF-A protein levels in the mice, but did not reduce macrophage recruitment, or change the mRNA abundance of placental or platelet-derived growth factors.
Takeaway.
Study author Jayakrishna Ambati, MD, stated that the discovery finally answers a longstanding question about how ocular immune cells—such as macrophages—contribute to abnormal blood vessel growth under the retina.
Significance?
The findings offer a new direction for the research and development of more cost-efficient, effective, and accessible treatments for neovascular age-related macular degeneration (wet AMD), proliferative diabetic retinopathy (PDR), ischemic retinal vein occlusion (RVO), and other diseases affecting millions of patients worldwide.