New Research on Autoimmune Response in Glaucoma

Approximately 70 million people around the world have glaucoma, however, little is known about the cause of the disease. An August 2018 article in MIT News published a recent study from the journal Nature Communications suggesting glaucoma may be an autoimmune condition.

The study, conducted by Massachusetts Institute of Technology (MIT) researchers in collaboration with Massachusetts Eye and Ear, found indications of an autoimmune connection for glaucoma in mice trials.

T cells’ role in the development of glaucoma

The research revealed the progressive deterioration of the retina, which is characteristic of glaucoma, is rooted in the body’s “helper” T cells. T cells are indispensable for the promotion of adaptive immunity. Adaptive immunity, part of the overall immune system, is a group of specialized cells that respond specifically to eliminate or prevent reoccurrence of pathogens by immunological memory. During the first encounter with a pathogen, long-lived memory T and B cells are established. When they encounter the same pathogen again, the memory cells are activated to unleash a more rapid protective response.

The MIT researchers found T cells seemingly attacking neurons in the retina. They hypothesized that the cause may be due to the cells’ earlier encounters with normally occurring bacteria in the human body.

Study indicates connection between autoimmune responses and eye disorders

In a 2011 article in Experimental Eye Research, a physician[A1] affiliated with the Department of Ophthalmology & Visual Sciences at the University of Texas Southwestern Medical Center noted approximately one-fourth of patients who develop glaucoma demonstrate normal intraocular pressure.

Researchers posited these individuals may have non-pressure-related conditions leading to stress on the optic nerve and retina, and contributing to disease of the optic nerve. These conditions include cardiovascular disease, atherosclerosis, migraines, genetic mutations and an aberrant immune response, which could indicate the presence of an autoimmune cause for neural deterioration.

Progressive nature of glaucoma may indicate immune response

Sometimes, even after patients with glaucoma were treated with medical interventions aimed at lowering intraocular pressure, some patients’ glaucoma symptoms worsened. According to the MIT researchers, the same phenomenon held true for the mice in their trials.

This observation led them to conclude the change in pressure itself was likely igniting a progressive condition, most likely a type of immune response.

Increased intraocular pressure and T cells in the eye

The researchers put their hypothesis to the test by searching for the presence of T cells in the retinas of the mice subjects. They did find the T cells in retinal tissue, which is an uncommon occurrence. The blood-retina barrier typically blocks T cells from entering the retina.

The scientists concluded that a rise in intraocular pressure results in T cells being able to overcome the barrier and enter the retina. Researchers went on to elevate eye pressure in mice without the T cells. In this group of mice, the elevated pressure produced miniscule retinal damage. After the intraocular pressure was normalized, no further retinal deterioration occurred.

T cells may target “heat shock” proteins

After investigating further, the MIT group discovered the T cells they had already linked to glaucoma are those which target “heat shock” proteins. These proteins assist cells in combating injuries and stresses.

Under normal circumstances, these T cells would not attack proteins produced by the host animal. But in this case, the scientists came to believe the T cells had come into earlier contact with bacterial heat shock proteins.

Previous bacterial contact may cause immune response triggered by intraocular pressure

A follow-up test helped to substantiate the developing hypothesis. The scientists attempted to facilitate the development of glaucoma in mice whose bodies did not contain the relevant bacteria. They discovered these mice remained glaucoma-free.

According to an article published on the Massachusetts Eye and Ear website, the immune cells which can develop in the eye as a response to previous bacterial contact are a significant cause of glaucoma-related vision loss. Elevations in intraocular pressure trigger an autoimmune response leading to the destruction of the eye’s neurons.

This outcome is analogous to a number of other types of immune responses initiated in response to bacterial infection.

Implications for future research and treatment of glaucoma and other diseases

The MIT News further described the next step in the project: to find out whether the phenomenon they had observed in mice would hold true in human beings. The research team studied humans with glaucoma and their expectations were confirmed. These patients displayed quantities of heat shock-specific T cells which were present at five times the normal level.

The results suggest this phenomenon can be generated by exposure to any set of bacteria which produce the type of T cells that attack heat shock-specific proteins. Among the ramifications of the project is the beginning of an investigation of whether the same type of process might set other neurodegenerative diseases in motion.

If so, techniques to block immune response could hold promise not only for new treatments for glaucoma, but possibly for other neurodegenerative conditions. The team plans additional studies to determine whether other components of immune system response can also play a role in the development of glaucoma.

Originally published at https://www.linkedin.com.