Findings from a study published today in Nature Communications indicate that glaucoma may be an autoimmune disorder, suggesting potential new ways to treat the disorder.
One of the major risk factors for glaucoma is elevated pressure in the eye. This can occur as people age and the ducts that allow fluid to drain become blocked. Current treatments often focus on lowering this intraocular pressure, but in many patients the disease worsens even after pressure is lowered.
Curious about what this pressure change might mean, researchers at MIT and Massachusetts Eye and Ear came up with the hypothesis that the pressure change might be an immune response.
To test the hypothesis, the researchers looked for immune cells in the retinas of a mouse model of glaucoma. This search revealed the presence of T cells, which are normally blocked from entering the retina by the blood-retina barrier. When intraocular pressure goes up, T cells appear to somehow be able to get through the barrier and into the retina.
Further investigation by an immunologist revealed that intraocular pressure generated in mice lacking T cells did induce a small amount of damage in the retina, but the disease progressed no further after eye pressure was returned to normal. They found that glaucoma-linked T cells target heat shock proteins, in spite of the fact that T cells should not target its own heat shock proteins.
To test if this self-targeting is due to previous exposure to bacterial proteins similar to the self-proteins, the researchers collaborated with an MIT lab whose team maintains mice with no bacteria. In the bacteria-free mice, the disease did not develop.
To see if these findings might be extrapolated to humans, glaucoma patients were tested and found to have five times the normal level of T cells specific to heat shock proteins. The researchers’ studies suggest that this effect is not specific to a particular bacterial strain of bacteria, but a combination of bacteria that generate T cells that target heat shock proteins.
In the future, the team plans to investigate if this phenomenon may underlie other neurodegenerative disorders. "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 Dong Feng Chen an associate professor of ophthalmology at Harvard Medical School and the Schepens Eye Research Institute of Massachusetts Eye and Ear.