Resume: Study revealed a previously unknown contribution to the harmful growth of blood vessels in the eye associated with AMD and other common vision disorders. The findings could lead to new treatments for people suffering from age-related macular degeneration and other vision disorders.
Source: University of Virginia
Scientists at UVA Health have discovered an unknown cause of the harmful growth of blood vessels in the eye, which could lead to new treatments for blinding macular degeneration and other common causes of vision loss.
UVAs Jayakrishna Ambati, MD, and Shao-bin Wang, Ph.D., and their colleagues have identified a novel target to suppress the formation of abnormal blood vessel cross-links associated with eye disorders such as neovascular age-related macular degeneration, proliferative diabetic retinopathy, and ischemic retinal vein occlusion .
“Our study has opened up the possibility of reducing aberrant blood vessel growth in eye disease by targeting the epigenetic machinery,” said Ambati, the founder and 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 better understanding of how ocular immune cells can cause a loss of control over the growth of blood vessels under the retina.
“This approach also provides a new direction for the development of more effective, cost-efficient and accessible interventions, avoiding issues such as drug resistance, which is a growing problem with conventional anti-VEGF therapies used in clinical treatments.”
Understanding vision loss
Scientists know that abnormal overgrowth of blood vessels in the eye is caused by excessive amounts of a substance called “vascular endothelial growth factor-A,” or VEGF, which plays an important role in blood vessel formation. Treatments are now available that target VEGF to prevent blood vessel overgrowth, and often provide dramatic benefits early on. Unfortunately, these benefits can fade over time. That leaves doctors needing better treatments to help preserve patients’ vision.
Ambati and Wang’s new research identifies a key protein that determines VEGF levels. Blocking this protein in laboratory mice significantly reduced their VEGF levels in a targeted manner without any unwanted side effects. For example, the scientists noted that they observed no toxic effects on the retina, the light-sensitive part of the eye where blood vessel growth occurs.
“This fat mass and obesity (FTO) protein has previously been found to be correlated 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 a long-standing question about how ocular immune cells, such as macrophages, contribute to abnormal blood vessel growth under the retina. This question was first explored by our team 20 years ago and we are thrilled to have found an answer.”
In addition to identifying a promising target for developing new treatments for vision loss, the discovery sheds important light on the fundamental mechanisms responsible for the overgrowth of blood vessels that robs millions of people of their sight.
Neurovascular age-related macular degeneration alone affects more than 200 million people worldwide. While much more research and testing will be needed before the new finding can be translated into a treatment, the UVA scientists are excited about the discovery’s potential.
“Current strategies for treating ocular neovascular disease, which mainly focus on regulating VEGF protein levels, are not perfect. Therefore, it is imperative to identify more targeted candidates to develop alternative therapies,” said Wang. “We are hopeful that our study will pave the way for the development of new treatments, ultimately reducing the burden of neovascular disease. “
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About this visual neuroscience research news
Author: Press Office
Source: University of Virginia
Contact: Press Service – University of Virginia
Image: The image is in the public domain
Original research: Open access.
“Targeting the m6A mRNA demethylase FTO suppresses vascular endothelial growth factor release and choroidal neovascularization” by Shao-bin Wang et al. Signal transduction and targeted therapy
Abstract
Targeting the m6A mRNA demethylase FTO suppresses vascular endothelial growth factor release and choroidal neovascularization
Vascular endothelial growth factor-A (VEGFA, also known as VEGF) is a critical angiogenic factor that regulates the physiological and pathological growth of blood vessels.
Increased abundance of VEGF in the eye underlies many forms of aberrant ocular angiogenesis and resulting vision loss, including in neovascular age-related macular degeneration (NvAMD), proliferative diabetic retinopathy (PDR), ischemic retinal vein occlusion, and retinopathy of prematurity (ROP). ). Several VEGF inhibitors are approved for such ocular angiogenic disorders. Despite the initial, and often dramatic, efficacy of anti-VEGF therapy, real-world and long-term studies are more sobering.
Thus, a better understanding of the regulation of ocular VEGF may further elucidate the underlying pathological mechanisms and help develop new therapeutic strategies.