Summary: A study has discovered a previously unknown contributor to the harmful growth of blood vessels in the eye associated with AMD and other common vision loss disorders. The findings could lead to new treatments for people with age-related macular degeneration and other vision loss disorders.
Source: University of Virginia
UVA Health scientists have discovered an unknown contributor to harmful blood vessel growth in the eye that could lead to new treatments for blinding macular degeneration and other common causes of vision loss.
UVA’s Jayakrishna Ambati, MD, and Shao-bin Wang, Ph.D., and colleagues have identified a new target to prevent the formation of abnormal blood vessel tangles associated with eye conditions such as macular degeneration age-related neovascular disease, proliferative diabetes retinopathy and ischemic retinal vein occlusion.
“Our study has opened up the possibility of mitigating aberrant blood vessel growth in eye disease by targeting the epigenetic machinery,” said Ambati, founding director of UVA’s Center for Advanced Vision Science and member of the Department of Medicine at UVA. ‘University of Virginia. Ophthalmology.
“Thanks to the local targeting of the epigenetic regulator, we have gained a better understanding of how ocular immune cells can lead to 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 issues such as drug resistance, which is a growing concern with conventional anti-VEGF therapies used in clinical treatment.
Understanding Vision Loss
Scientists know that abnormal vessel proliferation in the eye is fueled by excessive amounts of a substance called vascular endothelial growth factor-A, or VEGF, which plays an important role in the formation of blood vessels. There are now treatments that target VEGF to prevent vessel proliferation, and they often offer dramatic early benefits. Unfortunately, these benefits can fade over time. This leaves doctors in need of better treatments to help preserve patients’ sight.
New research from Ambati and Wang identifies a key protein that determines VEGF levels. Blocking this protein in lab mice dramatically reduced their VEGF levels in a targeted manner without adverse side effects. The scientists noted, for example, that they observed no toxic effects on the retina, the light-sensitive part of the eye where vessel proliferation occurs.
“This protein associated with fat mass and obesity (FTO) has already been shown 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,” Ambati said.
“This exciting discovery finally answers a long-standing question about how ocular immune cells, such as macrophages, contribute to the abnormal growth of blood vessels under the retina. This question was first investigated by our team 20 years ago, and we are glad to have found an answer.
In addition to identifying a promising target for the development of new treatments for vision loss, this discovery sheds important light on the fundamental mechanisms responsible for the proliferation 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 discovery can be translated into a treatment, UVA scientists are excited about the potential of the discovery.
“Current treatment strategies for ocular neovascular disorders, which primarily focus on regulating VEGF protein levels, are not perfect. Therefore, it is imperative to identify more targetable candidates to develop alternative therapies,” Wang said. “We hope 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 Office – University of Virginia
Picture: Image is in public domain
Original research: Free access.
“Targeting mRNA m6A demethylase FTO suppresses vascular endothelial growth factor release and choroidal neovascularization” by Shao-bin Wang et al. Signal transduction and targeted therapy
Abstract
Targeting FTO m6A demethylase mRNA 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.
The increased abundance of VEGF in the eye underlies many forms of aberrant ocular angiogenesis and consequent vision loss, including neovascular age-related macular degeneration (nvAMD), proliferative diabetic retinopathy ( PDR), ischemic retinal vein occlusion and retinopathy of prematurity (ROP). Multiple VEGF inhibitors are approved for such ocular angiogenic diseases. Despite the initial, and often dramatic, efficacy of anti-VEGF therapy, real-world and long-term studies are sobering.
Thus, a better understanding of the regulation of ocular VEGF may further elucidate the underlying pathological mechanisms and help to develop new therapeutic strategies.