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Early signs of Glaucoma found in the Brain

Submitted by on 23 March, 2019 – 4:32 am

Researchers at the Vanderbilt Eye Institute are now one step closer to deciphering the leading cause of blindness in the United States – glaucoma.

In a recent study, David Calkins, Ph.D., research director of the VEI, found the first sign of glaucoma damage actually occurs in the brain.

Glaucoma is usually considered a disease of the eye in which the sensitivity to eye pressure causes damage to the retina and optic nerve, which are components of the central nervous system do not regenerate. The damage starts in the peripheral visual field and moves toward the center resulting in complete blindness unless detected early. For this reason, the degeneration in glaucoma is often difficult to detect.

The report this week in the Proceedings of the National Academy of Sciences described the recent laboratory experiments in which Calkins shows that glaucoma is very similar to other central nervous system diseases.

“This is a paradigm shift in our thinking about this disease,” said Calkins, associate professor of ophthalmology at the IEV and a member of the neuroscience program. “This will have global implications. This information opens completely new domain of nerves derived therapeutics.”

The combination of this new understanding of neuronal injury that first for glaucoma occurs with the fact that the incidence of injury increases with age, researchers now have an idea of how the loss of sensory function occurs in the normal aging.

Traditionally, treatment of glaucoma have focused on reducing eye pressure in the eye. But the recent PNAS study gives credence to a new direction of study focused on neuronal activity in the center of the brain where the optic nerve of his first connections forms.

“This is a very interesting work that shows that we must take into account not only the eye but also the brain, in our efforts to understand diseases that cause blindness, like glaucoma,” said Paul Sternberg, MD, chair of Ophthalmology and Sciences VEI Visual and director. “We are optimistic that the neurobiological approach Dr. Calkins’ will lead to new targets for potential treatment of this devastating disease.”

Calkins explained that the age related diseases such as Alzheimer’s and Parkinson’s, the largest contributor to the susceptibility to neuronal damage is age.

“In these diseases, damage to neurons occurs very early in the projections distal death in a process called back. When he died back, neuronal axon loses its ability to communicate with the target.

“In the case of glaucoma, we have shown that axons in the optic nerve loses its ability to communicate with their projection site in the midbrain.

Calkins team hoped to find a loss of communication on the optic nerve of the eye, but what was also discovered that the connection between the optic nerve and brain was dying first.

Using animal models with high-pressure glaucoma, the team was able to see a very early mechanism of vision loss involves the loss of communication between the optic nerve and the midbrain, where sensory information about sound, heat , cold, pain and pressure source.

“If the disease has continued long enough, eventually, optic nerve, retina, showing signs of degeneration,” Calkins said. “So the degeneration of the works in reverse order. It starts in the brain and works its way back to the retina so that in the latter stages of the disease, the first structures, the closest to the eyes are the last to go. ”

Now the team is working on finding drugs that can improve or restore the connectivity between the optic nerve and midbrain. Using two synthetic compounds and natural growth factors of nerves in the brain, such as derived neurotrophic factor (BDNF), the team is exploring ways to restore road communication.

According to the National Eye projections for 2020, 80 million people worldwide have glaucoma. The risk of vision loss in glaucoma increases sevenfold after the age of 55.

Since 1915 there have been fewer than a dozen articles on glaucoma, published in PNAS, Calkins said.

“People thought we were crazy when we suggested that the first signs of injury for glaucoma were found in the brain,” he said. “What makes this discovery is that we can see the disease through the same lens that we consider other age-related neurodegenerative diseases.”

The study, which also introduces the possibility of using MRI as early diagnostic tool, was funded by the Foundation for Research on glaucoma and the National Eye Institute.

Sam Crish, Ph.D., staff scientist at the laboratory Calkins, is the first author.

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