Ophthalmologist and Physician-Scientist
Autoimmune Role in Glaucoma Progression

Autoimmune Role in Glaucoma Progression

Researchers have developed new technologies for diagnosing glaucoma earlier and treating the condition more effectively. However, medical professionals still do not fully understand the pathogenesis of the disease. For the nearly 70 million people around the world with glaucoma, uncovering the pathological processes causing it would be life changing.

In a recent study, researchers from Massachusetts Institute of Technology and Massachusetts Eye and Ear suggest an autoimmune component could be at play in certain forms of glaucoma, which is defined by an increase in intraocular pressure. The pressure compresses the retina and optic nerve and can cause irreversible vision loss. Their research found T cells within mice are actually responsible for the retinal degeneration associated with glaucoma. Moreover, the T cells were programmed to attack the retinal cells as a result of prior interaction with bacteria normally present within the human body.

What makes this discovery so exciting is the potential for new treatments for the disease. Inhibiting the autoimmune response could help slow or even stop disease progress.

Current Approaches to Glaucoma Treatment

Current treatments of glaucoma aim to reduce the pressure in the eye that builds up and results in glaucoma. The pressure can prove problematic because individuals often experience no symptoms until they begin to lose their vision.

For many patients, the increase in intraocular pressure is a result of aging. Over time, the ducts of the eye, which normally allow fluid to flow out, become blocked. The dilemma is many patients continue to experience deterioration of their vision even after intraocular pressure has been normalized. This could be explained by the findings of the recent study.

The researchers hypothesized increases in intraocular pressure were actually triggering a different, yet also progressive, pathological process. An immune response seemed to make the most sense given the circumstances of increased pressure.

The scientists examined the retinas of mice with glaucoma and found T cells. This was unusual since T cells, part of the adaptive immune system, are generally blocked from entering the retina through the tight junctions of the blood-retina barrier. The barrier helps suppress inflammation in the eye, which can lead to further damage to delicate structures. However, in the glaucomatous state, T cells somehow gain the ability to enter the retina.

Laboratory study

Specific T Cell Response in Glaucoma

The research team brought in an immunologist to further investigate the role of the T cells and their potential contribution to the pathology of glaucoma. Researchers found mice without any T cells experienced a different pathological progression of glaucoma.

While increases in intraocular pressure in the mice did cause damage to the retina, destruction did not continue once eye pressure was normalized. Analysis of the T cells involved in retinal invasion found they targeted heat shock proteins, which normally play a key role in stress responses.

T cells should not react to host proteins. It is possible these T cells were induced to attack because of prior exposure to heat shock proteins of bacteria. These proteins are similar across species, which means cross-reaction is quite common. Germ-free mice did not develop glaucoma when researchers attempted to induce it, which supports this hypothesis.

Finally, the researchers attempted to determine if the same process was happening in humans. They found patients with glaucoma had five times more T cells specific to heat shock proteins than other individuals. Moving forward, the scientists hope to identify other components of the immune system that might have a role in this autoimmune process.

In addition, it is possible a similar phenomenon is at play in other degenerative disorders, especially neurological ones. The team believes the treatments which may be derived from this research could potentially benefit patients with a variety of different brain diseases. The immune component could also be used as a screening or testing mechanism to determine the probability of disease.

Potential Treatments and Prevention Mechanisms

In terms of potential treatments, the researchers recognize many different pathogens in the human body can produce heat shock protein. This means it could be difficult to prevent T cells from being sensitized to them. However, it may be possible to develop treatments specifically targeted to these activated T cells and prevent them from doing damage to the retina.

Blocking the autoimmune response altogether could also be considered a means of prevention in patients who are at particularly high risk of developing glaucoma. Moving forward, it will be exciting to see what other immune system components get implicated in this autoimmune response and how biological agents can be engineered to block their effect.