Do Pressure Sensors Fail in Glaucoma? A BrightFocus-funded Hypothesis

Martha Snyder Taggart, BrightFocus Editor, Science Communications
  • Science News
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Technical slide showing caveolae, flask-shaped pouches
The top images show the pouch-like openings that caveolins form in the outflow pathway of human eye. In the lower panel: electron micrograph showing numerous caveolae in Schlemm’s canal of mouse. | Courtesy of Michael Elliott, PhD

Michael Elliott, PhD, of the University of Oklahoma Health Sciences Center, continues to make rich discoveries about pressure-sensing cells in glaucoma.

In 2014, Elliott found that a gene known as CAV1 is expressed in the eye and linked with the presence of caveolae, or flask-shaped pouches that open into blood vessels.

“In cells where they’re abundant, caveolae act like springs; they can sense pressure in the cell,” Elliott reported, whereas in a mouse model without CAV1, the membrane loses its ability to respond to pressure. He hypothesized that caveolae act as sensors to regulate fluid drainage in the eye, sending signals to drain more fluid if intraocular pressure (IOP) increases, and to resist drainage if IOP is too low.

At the time, no one had investigated caveolae closely in the eye. With an NGR grant, Elliott found collaborators, including Ernst Tamm, PhD (University of Regensburg, Germany) an authority on outflow anatomy, and Dan Stamer, PhD (Duke University), whose expertise lies in measuring outflow. Together, they began to image and characterize caveolae’ response to pressure in the eye. The team carried out studies, and published results—acknowledging BrightFocus support—in a major journal (Stamer et al, Scientific Reports, 2016).

More recently, Elliott discovered that in mice models, abnormalities in CAV1 impact regulation of endothelial nitric oxide synthase (eNOS) in Schlemm’s canal, the final leg of the eye’s drainage pathway, where fluid is discharged into blood vessels. eNOS is a building block for nitric oxide, a molecule that dilates blood vessels and reduces blood pressure.

Elliott presented these results in his talk at “Basic Science Catalyzing Treatments for Glaucoma,” a 2017 Glaucoma Symposium sponsored by BrightFocus, the International Society for Eye Research (ISER), and others.

Elliott also is studying a related gene of interest, CAV2. In humans, irregularities in the CAV1/2 genes are associated with higher risk of developing primary open angle glaucoma--and Elliott’s work tentatively suggests why.

More exploration is needed, and if the same interplay between CAV1/2 genes and eye drainage is found in humans (as in mice), the pathway could become a new therapeutic target. Unlike current therapies, which only treat elevated IOP, this one might attack the cause.

Elliott’s funding expanded from his original 2013-15 NGR grant to include support from the National Eye Institute and others. Still, like any lab, he and his colleagues must constantly apply for new grants to support new projects.

Nonetheless he remembers being a lone researcher at the brink of these discoveries, and ended his Atlanta talk with thanks to BrightFocus “for allowing me to get this project going.”

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