Scientists have uncovered a previously unknown contributor to impaired blood vessel formation in the eye, which may lead to new treatments for blinding macular degeneration and other common causes of vision loss. The researchers published their findings in the scientific journal Signal Transduction & Targeted Therapy.
Jayakrishna Ambati, MD, and Shao-bin Wang, PhD, and their colleagues at UVA have identified a new target to prevent the formation of abnormal blood vessel tangles associated with eye conditions such as neovascular age-related macular degeneration, proliferative diabetic retinopathy, and ischemia. retinal vein occlusion.
“Our study opens up the possibility of mitigating abnormal blood vessel growth in eye diseases by targeting epigenetic mechanisms,” said Ambati, founding director of UVA’s Center for Advanced Vision Sciences and a faculty member at the University of Virginia School of Medicine. Ophthalmology.
“Through local targeting of an epigenetic regulator, we have gained a deeper understanding of how ocular immune cells can cause a loss of control over the growth of blood vessels under the retina.” This approach also offers a new direction for the development of more effective, cost-effective and accessible interventions, thereby avoiding problems such as drug resistance, a growing problem with conventional anti-VEGF therapies used in clinical treatment.
Understanding vision loss
Scientists knew that abnormal blood vessel growth in the eye was driven by excess amounts of a substance called “vascular endothelial growth factor-A,” or VEGF, which plays an important role in blood vessel formation. Treatments that target VEGF to prevent vessel overgrowth are now available and often provide dramatic benefits initially. Unfortunately, these benefits can fade over time. This means doctors need better treatments to help preserve patients’ vision.
VEGF levels
New research by Ambati and Wang identifies a key protein that determines VEGF levels. Blocking this protein in lab mice significantly reduced their VEGF levels, in a targeted manner, without unwanted side effects. For example, the researchers noted that they observed no toxic effects on the retina, the light-sensing part of the eye where blood vessel overgrowth occurs. This fat mass and obesity-associated protein (FTO) have previously been shown to correlate with obesity in humans.
Unexpectedly, we found that it also plays an important role in regulating ocular neovascularization through an epigenetic mechanism,” said Ambati. “This exciting discovery finally answers the long-standing question of how ocular immune cells, such as macrophages, contribute to the abnormal growth of blood vessels beneath the retina.” This question was first explored by our team 20 years ago and we are thrilled to have found the answer.”
In addition to identifying a promising target for the development of new treatments for vision loss, the discovery sheds important light on the underlying mechanisms responsible for the overgrowth of blood vessels that robs millions of people of their sight. Age-related neurovascular macular degeneration alone affects more than 200 million people worldwide. While much more research and testing will be needed before the new findings can be translated into treatment, UVA scientists are excited about the discovery’s potential.
“Current treatment strategies for ocular neovascular disorders, which primarily focus on regulating VEGF protein levels, are not perfect. Therefore, it is essential to identify more targeted candidates for the development of alternative therapies,” said Wang. “We hope that our study will pave the way for the development of new treatments , which will ultimately reduce the disease burden associated with neovascular diseases.”
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