Preventing Glaucoma By Unclogging The Eye’s ‘Drainage Canals’

Researchers in Korea have identified the molecular pathway causing fluid build-up in the eyes, a discovery that could lead leading to a treatment for glaucoma.

AsianScientist (Sep. 26, 2017) – In a study published in the Journal of Clinical Investigation, a group of researchers in Korea have discovered how fluid builds up within the eye during glaucoma, allowing them to suggest a potential therapy for the age-related eye condition.

Glaucoma is the second cause of irreversible blindness, after cataracts. It affects about 3.5 percent of the world population aged 40 to 80. One of the most important risk factors for glaucoma is the increased pressure inside the eye. A liquid called aqueous humor is constantly produced and drained out from the eye. It transports nutrients and inflates the eye, giving it a roughly spherical shape.

However, if this fluid cannot flow out of the eye chambers freely, an increase in intraocular pressure can damage the optic nerve, leading to vision loss. The precise mechanism of elevated resistance to aqueous humor outflow remains unclear. Although the current treatments for glaucoma tackle the production and outflow of aqueous humor, their outcomes are still poor.

A component of the eye that plays a fundamental role in draining out the aqueous humor is the Schlemm’s canal. It collects the aqueous humor and mediates its transfer from the eye chambers into the blood circulation. The cells on the walls of the canal, endothelial cells, ship the liquid from the inner to the outer side in ‘packages,’ called vacuoles. As the shape and number of the vacuoles reflect the outflow performance, several giant vacuoles are expected in the normal outflow process.

In this study, a research team led by Professor Koh Gou Young of the Graduate School of Medical Science and Engineering at the Korea Advanced Institute of Science and Technology showed that an important regulator of Schelmm’s canal functionality is the angiopoietin-Tie2 system. Angiopoietins, such as angiopoietins-1 and 2 (Ang1 and Ang2, respectively), are proteins important for the growth of new blood vessels, and Tie2 is the receptor that binds them.

The researchers reported that adult mice deficient in Tie2 suffer from elevated intraocular pressure, retinal neuronal damage and partial visual impairment. Moreover, they had a markedly decreased number of giant vacuoles inside Schlemm’s canal endothelial cells, which indicate poor aqueous humor drainage.

The scientists also investigated if and how this process changes in older mice, as aging is a major risk factor for glaucoma. They demonstrated that aged mice had fewer giant vacuoles and displayed reduced levels of Tie2, Ang1 and Ang2, as well as other proteins associated with the angiopoietin-Tie2 pathway, such as Prox1.

To verify whether Tie2 activation could improve eye drainage, the researchers tested the effect of an Ang2-binding and Tie2-activating antibody (ABTAA). They injected it into one eye of a mouse model of glaucoma, while the other eye of the same mouse functioned as the negative control.

After one week, levels of Tie2 and Prox1 in the ABTAA-treated eyes increased, and so did the number and diameter of giant vacuoles in Schlemm’s canals, compared to the negative control eyes. The researchers further observed a decrease in intraocular pressure when ABTAA was injected to the eyes of mice suffering from glaucoma with regressed Schlemm’s canals, indicating that this antibody might be considered as a therapeutic option.

“The slow development of glaucoma treatments is partly due to the poor understanding of the underlying pathogenesis,” said Koh, the corresponding author of the study. “We hope that by identifying the critical role of the angiopoietin-Tie2 system in adult Schlemm’s canals, we can boost the development of therapeutics for glaucoma.”

The article can be found at: Kim et al. (2017) Impaired Angiopoietin/Tie2 Signaling Compromises Schlemm’s Canal Integrity and Induces Glaucoma.


Source: Korea Advanced Institute of Science and Technology.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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