Glaucoma, a disease that afflicts nearly 70 million people worldwide and can lead to blindness, is something of a mystery despite its prevalence.
A new study from MIT and Massachusetts Eye and Ear has found that the disease, which damages the retina and optic nerve, may in fact be an autoimmune disorder. In a study of mice, the researchers showed that the body’s own T cells are responsible for the progressive retinal degeneration seen in glaucoma. Furthermore, these cells appear to be primed to attack retinal neurons as the result of previous interactions with bacteria that normally live in our body.
The discovery suggests that it could be possible to develop new treatments for glaucoma by blocking this autoimmune activity, the researchers say.
“This opens a new approach to prevent and treat glaucoma,” says Jianzhu Chen, an MIT professor of biology, a member of MIT’s Koch Institute for Integrative Cancer Research, and a senior author of the study, which appeared in Nature Communications.
One of the biggest risk factors for glaucoma is elevated pressure in the eye, which often occurs as people age and the ducts that allow fluid to drain from the eye become blocked. Most treatments focus on lowering this pressure, but in many cases, the disease worsens even after it returns to normal.
“That led us to the thought that this pressure change must be triggering something progressive, and the first thing that came to mind is that it has to be an immune response,” says Dong Feng Chen, an associate professor of ophthalmology at Harvard Medical School and the Schepens Eye Research Institute of Mass. Eye and Ear, who is also a senior author of the study.
Indeed, the researchers found immune cells in the retinas of mice that experienced elevated eye pressure. This is unusual because T cells are normally blocked from entering the retina. However, it appears that when eye pressure goes up, T cells are somehow able to get through the barrier that usually stops them.
The researchers then showed that in mice that lack T cells, increasing eye pressure induced a small amount of damage to the retina, but the disease did not progress further after pressure returned to normal.
Further studies revealed that the T cells target proteins called heat shock proteins, which help cells respond to stress or injury. Normally, T cells should not target proteins produced by the host, but the researchers found that these T cells had been previously exposed to bacterial heat shock proteins and could cross-react with human heat shock proteins, which are very similar.
The researchers also found that glaucoma patients have five times the normal level of T cells specific to heat shock proteins, suggesting that the same phenomenon may contribute to the disease in humans.