Genetically-Modified Occludin Shown to Protect Against Diabetes-Related Vision Loss Andreia Goncalves, Ph.D., a post-doctoral fellow working in the lab of David Antonetti, Ph.D., has demonstrated that triggering a single mutation in a specific protein building block of retinal blood vessels can help guard against the devastating visual consequences of diabetes. These consequential findings were published in July 2021 in the journal Diabetes. Diabetic retinopathy (DR) is one of the leading causes of vision loss and blindness. A hallmark of DR is vascular permeability, or leaks in the blood vessels of the retina. One of the mechanisms that drive vascular permeability is the action of one protein — vascular endothelial growth factor (VEGF), on another — occludin, a tight junction protein that binds cell membranes together to form nonpermeable barriers.
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Trainee Highlights
“We wanted to better understand the role of the neurovascular unit in diabetes — which represents the relationship between retinal neurons and blood vessels. Specifically, we wanted to find out if we could preserve vision by protecting occludin against the actions of VEGF, and as a result, maintain a proper barrier in the retinal blood vessels,” explains Dr. Goncalves. Her team accomplished that by introducing a genetic mutation in occludin in the retinal blood vessels of mice with diabetes. “With just one mutation in occludin, its functionality was preserved,” she says. “It provided complete protection against diabetes-induced permeability, and preserved visual acuity and contrast sensitivity. That demonstrates that a proper barrier in the retinal vessels is critical for visual function. It’s a very encouraging finding, emphasizing the importance of the neurovascular unit in diabetes.”
