The Eye's Hidden Drain, Discovered

For more than a century, the textbook view held that the eye sat outside the body’s lymphatic network. A team from the University of British Columbia (UBC) and the University of Toronto has now described a drainage route at the back of the eye that connects to it. They have named it the posterior ocular lymphatic outflow pathway, or POLO.

The work was carried out in mice, and the researchers are clear that how the pathway behaves in humans remains to be established. Even so, it gives scientists a new anatomical structure to examine in diseases that cause permanent sight loss, and a possible answer to a question that has gone unresolved for decades: how the retina gets rid of its waste.

Why the retina needs a drain

The retina converts light into signals the brain can read, and that takes a lot of energy. “The retina is one of the most metabolically active parts of the body, constantly generating byproducts that need to be cleared,” said Dr. Neeru Gupta, professor and head of UBC’s department of ophthalmology and visual sciences.

When fluid and waste build up, tissue can be damaged. Glaucoma, macular degeneration and other retinal disorders are all associated with changes in fluid regulation, cellular waste accumulation, tissue stress and inflammation. Age-related macular degeneration alone affects approximately 2.5 million Canadians. Until now, researchers have struggled to explain exactly how the back of the eye clears unwanted material.

Tracing the route

The eye was long considered to lack the lymphatic drainage found in nearly every other organ. That began to shift in 2009, when Gupta and Dr. Yeni Yücel identified a lymphatic-related route at the front of the eye, which they called the uveolymphatic pathway. Yücel, a professor and director of ophthalmic pathology at the University of Toronto, went on to ask whether similar routes existed elsewhere in the eye. The back of the eye, where some of the most serious vision-loss diseases occur, remained largely unexplored.

To find out, the team used magnetic resonance imaging (MRI), near-infrared fluorescence imaging and microscopic examination in mice. They placed fluorescent tracer molecules in a narrow space at the rear of the eye and followed where they went.

The tracers revealed tiny lymphatic vessels in the choroid, the blood vessel-rich layer beneath the retina that helps nourish the outer retina. Lymphatic vessels had not previously been established there. Fluid moved from the back of the eye into the surrounding orbital tissues, and within minutes the tracers reached nearby lymph nodes.

“Because lymphatic vessels in the choroid were thought not to exist, the team used multiple techniques to demonstrate both their presence and function,” added Yücel, a pathologist-scientist at St. Michael’s Hospital.

What this news could (and couldn't) mean

Several open questions stand between this finding and any clinical use. Researchers need to establish how the POLO pathway works in people, whether changes in its function contribute to eye disease, and whether its activity can be modified safely.

If those hurdles are cleared, the pathway could point in a few directions. One is therapies that improve fluid clearance and so reduce the buildup of substances linked to inflammation and tissue damage. Another is using the route to improve drug delivery to structures deep within the eye. It may also help researchers untangle how pressure, inflammation and fluid movement interact in glaucoma and age-related macular degeneration. These remain possibilities, not established treatments.

Gupta framed the question this way:

She added:

The findings were published in Translational Vision Science & Technology. The research was supported by the Canadian Institutes of Health Research, Glaucoma Research Society of Canada, Henry Farrugia Ophthalmology Research Fund, Canadian Space Agency, Dorothy Pitts Chair, Stephen M. Drance Chair, Thor and Nicky Eaton Research Fund, and Canada Foundation for Innovation Leaders Opportunity Fund.