Is Glaucoma a Brain Disease?

Pressure inside the brain may also influence glaucoma, and this article explores this new research.

Glaucoma is a disease of the optic nerve, which is the long “cable” that connects the cells that transmit all of the visual information from the retina to visual targets in the brain. Glaucoma is first and foremost an eye disease, and the initial damage to the optic nerve takes place in the eye. However, because the optic nerve is part of the central nervous system, one can certainly think of glaucoma affecting the brain. It is more appropriate to say that glaucoma is a neurodegenerative disease of the eye, although there are some influences of the brain on glaucoma and vice versa. In this article we will discuss some of the ways in which the optic nerve and brain interact in glaucoma.

Can Pressure Inside the Brain Influence Glaucoma?

While one of the major risk factors of glaucoma is elevated eye pressure, more recently scientists have discovered that the pressure inside the brain may also influence glaucoma. This may be particularly true in patients who have “normal pressure glaucoma.” The rationale is that when the pressures inside the brain are lower than normal, and the pressures in the eye are “normal,” the difference between these two pressures (also called the translaminar pressure gradient) may still cause damage to the optic nerve.

Several scientists who have received grants from BrightFocus Foundation are studying this hypothesis, including Dr. Brian Samuels, Dr. Michael Fautsch, and Dr. Peter P. De Deyn.

• Dr. Samuels’ research focuses on understanding which cells in the brain control eye pressure and brain pressure.
• Dr. Fautsch is developing an animal model to study how lower brain pressures may influence optic nerve health and the development of glaucoma.
• Dr. De Deyn is tackling this question from a different perspective. It has been known for some time that patients with Alzheimer’s disease may have changes in their optic nerves that mimic glaucoma. It is also known that Alzheimer’s patients have lower brain pressure. Dr. De Deyn’s team is studying the mechanisms by which patients with Alzheimer’s disease have increased risk of glaucoma.

All of these studies will help shed light on the impact of brain pressure on the development and progression of glaucoma, in particular “normal pressure glaucoma.” Indeed, perhaps in the future there will be treatments to influence brain pressure and thus glaucoma.

Do Changes in Retina Cells Affect the Brain?

Another area of active research is uncovering ways in which the degeneration of the retinal cells in glaucoma affects the visual pathways of the brain. Because the final step in neurodegeneration that causes glaucoma is death of the retinal ganglion cells of the optic nerve, it is perhaps not surprising that since these cells project all the way to the brain, that there would be changes in the cells of the brain as well.

• Funded in part by BrightFocus Foundation, Dr. David Calkins and his team have uncovered some of the very early changes that occur in the brain in response to elevated eye pressure. These include decreased function of the retinal ganglion cells in their visual targets of the brain (Study 1 | Study 2).
• Another team, funded by the BrightFocus Foundation and led by Dr. Kevin Chan, is developing new imaging techniques using MRI (magnetic resonance imaging) to study early changes in the visual system of the brain in glaucoma patients. They hope to uncover a noninvasive and comprehensive way to evaluate the effect of chronic high eye pressures on the structures of the brain involved in processing vision.

A complete understanding of how the visual pathways are affected early in glaucoma neurodegeneration will help investigators identify new targets for treatment and better ways to detect glaucoma progression.

Glaucoma and Alzheimer’s: Is There a Connection?

Does glaucoma share any common degeneration pathways with other neurodegenerative diseases of the brain, such as Alzheimer’s disease? This is another area of active investigation and BrightFocus-funded researchers, Dr. Stuart McKinnon, Dr. Ian Trounce, and Dr. John Wood have all contributed to this area.

• Dr. McKinnon has published studies on the role of several abnormal proteins that are found in the brains of Alzheimer’s disease patients, including amyloid beta, on the retinal ganglion cells that die in glaucoma.
• Dr. Trounce and his colleagues have studied another Alzheimer’s disease protein in more detail, specifically amyloid precursor protein. Their research focuses on the effect of age and elevated eye pressure on amyloid precursor protein breakdown and whether restoration of this protein may actually protect the optic nerve from injury.
• Most recently, Dr. Wood was funded to study yet another Alzheimer’s disease protein, called tau. His work suggests that the characteristic changes in the tau protein that occur in Alzheimer’s disease, also occur in glaucoma.

All of these studies bring together what is known about the mechanisms underlying Alzheimer’s disease and applies it to glaucoma, in hopes of identifying new targets for treatment.

Summary

So, is glaucoma a brain disease? Certainly, glaucoma is a disease of the optic nerve, which can be considered an extension of the brain. And the optic nerve and brain influence each other in the neurodegenerative processes that result in glaucoma. By studying changes in the optic nerve and the brain, researchers will advance our understanding of glaucoma and develop new ways to diagnose, assess, and treat this potentially blinding disease.