Glaucoma is the leading cause of irreversible blindness, affecting almost 70 million people worldwide. Increased internal eye pressure (intraocular pressure, or IOP) has been the most significant known cause of glaucoma—as well as the primary target for treatment—but several questions have remained unanswered.

• How does IOP actually cause the damage on cellular and molecular levels?
• Why do some people with normal eye pressure develop glaucoma?
• Why does degeneration of the optic nerve and retinal ganglion cells persist, and even worsen, in some patients (especially when their IOP is returned to a normal range through treatment)? 

A recent collaborative study by scientists from MIT (Massachusetts Institute of Technology) and Massachusetts Eye and Ear sheds some light on these questions and explores the possibility that glaucoma may be an autoimmune disease.*

Background

T-cells, or T-lymphocytes, are one of the main components of the adaptive immune system. They kill infected host cells, activate other immune system cells, and help regulate our immune response. T-cells are not normally found in the retina, being blocked by a layer of cells called the blood-retina barrier, to avoid inflaming the eye under stress.

Studies involving rodents revealed that even a brief elevation of IOP was sufficient to allow T-cells to penetrate the blood-retina barrier. The infiltration led to progressive retinal ganglion cell (RGC) degeneration, even after the rodents’ IOP was normalized. 

One hypothesis was that the stress caused by elevated IOP set off a secondary immune or autoimmune response and this response is what led to continued RGC damage after the IOP was lowered. 

What they did 

To explore what role these T-cells may play in glaucoma, the researchers attempted to induce glaucoma in mice that were germ-free (lacking T-cells) by elevating the mice’s IOP. 

They discovered that: 

• Elevated pressure resulted in only minor damage to the retina.
• The damage did not progress after eye pressure returned to normal.

Further studies revealed that the specific T-cells linked to glaucoma are those that target heat shock proteins (HSPs). Our bodies produce HSPs to help cells respond to injury or stress and facilitate recovery. 

Normally, T-cells don’t target proteins that are produced by the host, but the researchers hypothesized that these particular T-cells had prior exposure to bacterial heat shock proteins. While the mice lacking T-cells failed to develop the disease, human patients with glaucoma were found to have five times the normal level of T-cells that target HSPs.

What they found

Results of the mouse study provide evidence that the body’s own immune system is responsible for the progressive retinal damage observed in glaucoma. Previous exposure to bacteria that naturally live in our bodies seems to have programmed these T-cells to attack retinal nerves. Blocking this autoimmune activity “opens a new approach to prevent and treat glaucoma,” says Jianzhu Chen, professor of biology at the Massachusetts Institute of Technology (MIT).

What this means

The findings suggest areas for further research, including:

• Whether or not other components of the immune system may be at work in the inception and progression of glaucoma
• Whether or not this anomalous autoimmune response underlies other neurodegenerative disorders

According to Dong Feng Chen, associate professor of ophthalmology at Harvard Medical School and the Schepens Eye Research Institute of Massachusetts Eye and Ear, the results of this latest study could have impacts that transcend glaucoma.

“What we learn from the eye can be applied to the brain diseases,” said Chen, “and may eventually help develop new methods of treatment and diagnosis.”

The full study, “Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma,” can be found on the Nature Communications website.

*Trafton, A. (2018, Aug. 10). “Study suggests glaucoma may be an autoimmune disease.” MIT News.

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