Unexpected findings expose glaucoma as autoimmune disease

The body’s own immune system destroys retinal cells and drives glaucomatous neurodegeneration, researchers reported August 10 in the journal Nature Communications.

The surprise finding came from a mouse study performed by scientists from MIT and Massachusetts Eye and Ear. They found that T cells, primed by interactions with the body’s normal bacterial flora, launch an attack on retinal neurons. Gradually, this attack wears away at the retina and optic nerve, causing blindness.

“This opens a new approach to prevent and treat glaucoma,” senior author Jianzhu Chen, PhD, a professor of biology at MIT, told MIT News. Therapies that block this autoimmune attack could theoretically stall glaucoma progression, he noted.

The study originated from the well-documented observation that glaucoma can continue to progress after stabilizing a patient’s IOP. The researchers hypothesized that the pressure change might somehow trigger a wayward immune response, which could then cause persistent degeneration. 

Not only did the team find T cells in the retina of mice with glaucoma—a surprising discovery, as immune cells are normally turned away at the blood-retina barrier—but they further showed that the barrier is lifted during brief periods of elevated IOP, allowing these T cells to pass through.

Once inside the retina, T cells that have previously encountered bacterial stress proteins begin attacking similar stress proteins produced by retinal ganglion cells. This mistaken attack destroys the neurons and leads to glaucoma.

Indeed, humans with glaucoma harbor 5-fold more of these wayward T cells in their blood than humans without glaucoma, the researchers found. The team is exploring whether additional immune molecules contribute to this destructive process, and whether a similar autoimmune process may underlie other neurodegenerative conditions.

“What we learn from the eye can be applied to the brain diseases, and may eventually help develop new methods of treatment and diagnosis,” said senior investigator Dong Feng Chen, MD, PhD, an associate professor of ophthalmology at Harvard Medical School and the Schepens Eye Research Institute of Massachusetts Eye and Ear.