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UVA Researchers Discover Potential New Way to Prevent Vision Loss

UVA Researchers Discover Potential New Way to Prevent Vision Loss

February 23, 2023

Researchers at UVA Health, including Jayakrishna Ambati, MD, and Shao-bin Wang, PhD, have discovered a new cause of harmful blood vessel growth in the eye that could pave the way for the development of new treatments for macular degeneration and other common causes of vision loss.

The researchers have published their findings in the scientific journal Signal Transduction & Targeted Therapy

The team has identified a new target that could be used to prevent the formation of abnormal tangles of blood vessels, which are linked to eye conditions like neovascular age-related macular degeneration, proliferative diabetic retinopathy, and ischemic retinal vein occlusion.

“Our study has opened up the possibility of mitigating aberrant blood vessel growth in eye diseases by targeting the epigenetic machinery,” said Ambati, the founding director of UVA’s Center for Advanced Vision Science and a member of the University of Virginia School of Medicine’s Department of Ophthalmology.

“Through local targeting of the epigenetic regulator, we have gained a deeper understanding of how ocular immune cells can cause a loss of control over blood vessel growth under the retina. This approach also offers a new direction for the development of more effective, cost-efficient and accessible interventions, thereby avoiding issues such as drug resistance, which is a growing concern with conventional anti-VEGF therapies used in clinical treatments.”

Understanding Vision Loss

Excessive amounts of vascular endothelial growth factor-A (VEGF) contribute to abnormal vessel overgrowth in the eye, which has been a known cause of vision loss. Treatments that target VEGF are available to prevent vessel overgrowth, and have been known to provide significant benefits at first. However, the efficacy of these treatments can diminish over time, leaving doctors in search of better options to preserve patients' eyesight.

The latest research by Ambati and Wang has discovered a crucial protein that regulates VEGF levels. In laboratory mice, inhibiting this protein led to a considerable reduction in VEGF levels. The study found that the protein blockade was selective and did not cause any negative side effects, as there were no observable toxic impacts on the retina, which is the area of the eye where the abnormal vessel overgrowth occurs.

“This fat mass and obesity-associated (FTO) protein was previously shown to be correlated with obesity in humans. Unexpectedly, we found it also play important roles in regulating ocular neovascularization through an epigenetic mechanism,” Ambati said. “This exciting discovery finally answers a longstanding question about how ocular immune cells, such as macrophages, contribute to abnormal blood vessel growth under the retina. This question was first investigated by our team 20 years ago, and we're thrilled to have found an answer.”

The discovery made by Ambati and Wang holds potential for the development of new treatments to address vision loss caused by blood vessel overgrowth. Additionally, this research provides valuable insights into the underlying mechanisms that lead to this condition, which affects more than 200 million people worldwide in the case of neurovascular age-related macular degeneration alone. Although further research and testing are required to apply these findings to treatment, the scientists are optimistic about the possibilities that their discovery may offer.

“Current strategies for treating ocular neovascular disorders, which primarily focus on regulating the protein levels of VEGF, are not perfect. Therefore, it is imperative to identify more targetable candidates to develop alternative therapies,” Wang said. “We are hopeful that our study will pave the way for the development of new treatments, ultimately reducing the burden of neovascular-related illnesses.”