"Just imagine if we could grow a bigger Schlemm's canal in anybody with glaucoma to lower the pressure in the eye," says Susan Quaggin. "That's what we're hoping for with this new eye drop." (Credit: Eli Brody/Flickr)


Glaucoma discovery inspires nanofiber eye drop

Having discovered a new cause of glaucoma in mice, scientists are working on a nanofiber eye drop to one day cure the disease in humans.

A cure for glaucoma, a leading cause of blindness in the United States, has been elusive because the basis of the disease is poorly understood.

In glaucoma, pressure builds from poor drainage of fluid from the anterior chamber of the eye, destroying retinal ganglion cells and eventually the optic nerve. The eye becomes like a bathtub that can’t drain because the pipe is clogged.

The clogged or defective vessel, known as Schlemm’s canal, is part of the lymphatic system that is essential for drainage in the eye.

The new study identifies the molecular building blocks needed to make the “drainage” vessels, providing the necessary chemical tools to repair the eye’s plumbing and restore normal drainage. Up until now, the molecular basis of the disease caused by an absent or defective canal was unknown.

The study appears in the Journal of Clinical Investigation.

Grow new ‘pipes’

“This is a big step forward in understanding the cause of the disease that steals the eyesight from 60 million people worldwide,” says senior study author and nephrologist Susan Quaggin of Northwestern Medicine. “This gives us a foothold to develop new treatments.”


“Our goal now is to grow new ‘pipes’ or vessels to cure the glaucoma,” says Quaggin.

The findings are based on a new mouse model of glaucoma developed by Quaggin and doctoral student Ben Thomson, which is one of the first animal models of the disease. Quaggin expects the animal findings to be relevant in human glaucoma.

Quaggin and colleagues are working to develop a nanofiber eye drop that activates regrowth of the clogged vessel.

“We are developing a highly potent peptide nanostructure that has the capacity to interact with many receptors at the same time,” says Samuel Stupp, professor of chemistry, materials science and engineering, and medicine.

“This will amplify the required signaling pathway for an effective therapy. The nanostructure is also being designed to have the necessary half-life to optimize efficacy.”

“Just imagine if we could grow a bigger Schlemm’s canal in anybody with glaucoma to lower the pressure in the eye,” Quaggin says. “That’s what we’re hoping for with this new eye drop.”

Glaucoma’s mouse model

The new study identifies a critical chemical signaling pathway for the healthy functioning of the Schlemm’s canal and the substances necessary for its growth and development.

That pathway requires the chemical equivalent of a lock and key to open. The lock is a substance called Tie2 and the key is a growth factor called angiopoietin. The scientists discovered if either the key (angiopoeitin) or the lock (Tie2) is missing in mice, they can’t make Schlemm’s canals and will develop glaucoma.

Both these substances are necessary to unlock the pathway to a cascade of events inside the cell that produce the canals.

“We really nailed that pathway as being critical,” Quaggin says. “Now we know these two substances are key factors in the development of glaucoma, which wasn’t known before.”

The lock and key are likely to be involved in human glaucoma, Quaggin notes. “The mouse model is so similar to what we see in patients with glaucoma,” she says.

The animal model of glaucoma now will enable scientists to study treatments as well as how glaucoma develops.

“Now we can understand how raised pressure leads to the damage of the neurons in the optic nerve,” Quaggin says.

The National Eye Institute/National Institutes of Health, the Canadian Institutes of Health Research, and Terry Fox Foundation supported the research.

Source: Northwestern University

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