Implicating Glymphatic System Dysfunction in Glaucoma

There is growing interest in the systems of drainage that carry away cerebrospinal fluid and molecular waste from the brain. The failure of these systems due to the damage and dysfunction of aging may be an important cause of neurodegenerative conditions, allowing protein aggregates such as amyloid-β to build up to pathological levels in brain tissue. One branch of this work is focused on drainage through the cribriform plate, while another is focused on the comparatively recently discovered glymphatic system. Here, researchers note that a portion of the glymphatic system is implicated in glaucoma, a retinal degeneration that is proximately caused by rising pressure in the eyeball. Underlying causes are thought to include autoimmunity, senescent cells, and chronic inflammation in general.

Instead of a traditional lymphatic system, the brain harbors a so-called glymphatic system, a network of tunnels surrounding arteries and veins through which fluid enters and waste products drain from the brain. In a new study researchers show that the rodent eye also has a glymphatic system that takes out the trash through spaces surrounding the veins within the optic nerve. They also found that this system may be compromised in glaucoma and is capable of clearing amyloid-β, the build up of which has been implicated in the development of Alzheimer's disease, glaucoma, and age-related macular degeneration.

The majority of the aqueous humor - the fluid that fills the chamber between the cornea and the lens - drains from the eye to the surrounding vasculature through a circular lymph-like vessel called Schlemm's canal. This helps regulate intraocular pressure. Researchers decided to connect the knowledge about the front of the eye with their questions about the back of the eye. Because a 2012 study that the brain's glymphatic system was capable of clearing amyloid-β, they used that molecule to investigate the existence of an ocular glymphatic system.

The researchers found that the constriction of the pupil in response to light in both mice and rats increased glymphatic clearance from the eye. They also showed that the pressure in the eye, which is higher than that in the cranium, is necessary to drive the drainage through the ocular glymphatic system. Because of this, they hypothesized that glymphatic clearance might also be disrupted in glaucoma, a disease that typically involves increased intraocular pressure.

The research team determined that there was more amyloid-β clearance from the eyes of two different mouse models of glaucoma than from age-matched control mice. But the increased drainage did not seem to be caused by changes in intraocular pressure. Instead, excessive outflow was actually leakage into the spaces between axons in the optic nerve, not into the glymphatic system, that was related to a breakdown in the barrier between the eye and the optic nerve. The researchers hypothesized that this barrier normally diverts fluid, facilitating solute transport along the optic nerve's veins, a process that may fall apart in a diseased eye.

Link: https://www.the-scientist.com/news-opinion/quasi-lymphatic-system-in-the-rodent-eye-clears-waste-67430

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