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University of Virginia Researchers Discover New Target to Prevent Vision Loss

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The discovery of a protein that determines levels of vascular endothelial growth factor-A (VEGF) could lead to new therapies for macular degeneration, diabetic retinopathy and other common causes of vision loss.

Researchers at the University of Virginia Health School of Medicine have found a key protein that determines levels of vascular endothelial growth factor-A (VEGF), which plays an important role in blood vessel formation. VEGF is often involved in abnormal vessel growth in the eye, leading to macular degeneration, diabetic retinopathy and other common causes of vision loss.

Jayakrishna Ambati, M.D.

Jayakrishna Ambati, M.D.

UVA’s Jayakrishna Ambati, M.D., and Shao-bin Wang, Ph.D., and their colleagues have found that blocking this protein in lab mice reduced their VEGF levels significantly, and it did so in a targeted way, without unwanted side effects. This discovery could lead to new treatments for macular degeneration and other common causes of vision loss.

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

“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,” 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, said in a press release. 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.”

Several anti-VEGF therapies are currently available, including Avastin, Lucentis, Eylea. Genentech’s Avastin (bevacizumab) is indicated to treat patients with several cancers, but is used off-label to treat age-related macular degeneration. Genentech’s Lucentis (ranibizumab) and Regeneron’s Eylea (aflibercept) are both approved to several indications, including: age-related macular degeneration, diabetic retinopathy, and macular edema.

These therapies, however, require repeated treatments over time and, one study found that many patients stop treatment over time.

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

In addition to identifying a promising target for the development of new treatments for vision loss, Ambati and Wang’s research provides information on fundamental mechanisms responsible for the blood vessel overgrowth. They studied the role of m6A methyltranscriptome and the FTO protein. They found that inhibition of FTO suppressed VEGF protein levels and suppressed the release of VEGFA in human cell. FTO regulation, they said, is a previously undescribed role in VEGFA expression, providing a possible new for angiogenic eye diseases.

The research was supported by the National Institutes of Health.

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