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What Causes Glaucoma? Scientists May Have Finally Figured It Out

April 16, 2019 By Helly Bartolome Hernandez Marin, MD

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Glaucoma affects 70 million people worldwide, making it the most prevalent neurodegenerative disease and one of the leading causes of irreversible blindness. The disease is characterized by the progressive degeneration of the cells of the retina and the optic nerve.

Although glaucoma is a very common disease throughout the world, little is known about what causes it. Previously, it was thought that the only factor involved in the development of glaucoma was the increase in intraocular pressure (IOP). Although intraocular pressure is the main risk factor, several studies have been conducted in recent years in which it was observed that some patients with normal intraocular pressure developed a glaucomatous degeneration of the retina. Also, patients whose IOP is effectively controlled by medical treatment often continue to suffer progressive loss of vision, suggesting that additional mechanisms of damage exist.

A new study from the Massachusetts Institute of Technology (MIT) and Massachusetts Eye and Ear has discovered that an autoimmune mechanism may be involved in the development of this disease. In a study of mice, the researchers showed that the body's own T cells, which are part of the immune system, are responsible for the progressive retinal degeneration seen in glaucoma.

This research allows us to conclude that it would be possible to implement new therapeutic measures by blocking this autoimmune activity. "This allows us to establish a new approach for the treatment and prevention of glaucoma," said Jianzhu Chen, a professor of biology at MIT, and one of the study's lead authors.

T cells and bacteria

The increase in intraocular pressure occurs as people age, due to a blockage of the ducts that allow the flow of fluid contained in the eye. The disease generally is not detected at the beginning; patients may not realize they suffer from it until half of their ganglion cells in the retina have been lost.

Most current treatments for glaucoma are aimed at decreasing intraocular pressure; however, in many patients, the disease continues to progress even after the intraocular pressure returns to normal. The studies carried out showed that this situation also occurs in mice.

"That led us to the thought that this increase in intraocular pressure should trigger progressive changes in the retinal tissue, and the first explanation that occurred to me is that they have to be involved an autoimmune response," says Dong Feng Chen, associate professor of ophthalmology at the Harvard Medical School.

To test this hypothesis, the researchers looked for the presence of T cells in the retina of these mice and found that, in fact, there were immune cells inside the retina, something unusual due to the action of a retinal cell barrier that suppresses inflammation of the eye.

The researchers found that, with increased intraocular pressure, the T cells manage to cross this barrier and reach the retina. During the study, the researchers generated an increase in intraocular pressure in mice lacking T cells and found that while increased intraocular pressure causes damage to the retina, once the IOP returns to normal values, the progression of the disease stops.

Previous studies revealed that T cells linked to glaucoma act against proteins called heat shock proteins, which help cells respond to stress or injury. Normally, T cells should not attack the proteins produced by the host, but the researchers suspected that previous exposure to bacterial heat shock proteins could induce this action.

Human applications

After these findings in mice, researchers turned to humans with glaucoma and found that these patients had five times the normal level of T cells specific for heat shock proteins, which suggests that this phenomenon may also contribute to the disease in humans.

So far, the researchers' studies suggest that the effect is not specific to a particular species of bacteria, but that exposure to a combination of bacteria can generate T cells that act against heat shock proteins.

One question that the researchers plan to clarify is whether there are other components of the immune system that are involved in the development of glaucoma. They are also investigating the possibility that this phenomenon may be the basis of other neurodegenerative disorders and ways to treat such disorders by blocking the autoimmune response.

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