Gut bacteria may provide the trigger for autoimmune uveitis, a destructive inflammation of the eye, researchers at the US National Eye Institute (NEI) reported in a study published today (August 18) in Immunity. Autoimmune uveitis is a painful condition that can lead to debilitating blindness. It often hits adults 20 to 60 years old, and is responsible for up to 15 percent of all blindness and severe visual impairment in developed countries.

Researchers believe activated retina-specific T cells attack the eye, causing the inflammation, but the antigen that activates those T cells lies inside the normally immune-privileged eye, meaning T cells are not able to circulate in that area. How those T cells become activated without exposure to the eye has been poorly understood. The NEI’s Reiko Horai,Rachel Caspi, and their colleagues used a mouse model prone to developing uveitis and found that the animals’ intestines showed signs of increased T cell activation prior to the onset of uveitis.

“It’s the first study to show the potential of the microbiome to induce an autoimmune disease specific to the eye,” said Andrew Taylor, an ocular immunologist at the Boston University School of Medicine who was not involved in the research.

The team also found that the model mouse intestines showed high levels of interleukin-17A, a proinflammatory cytokine produced by T cells. In another experiment, the researchers administered a wide-spectrum antibiotic cocktail to the mice in an effort to reduce the gut microbiome. The antibiotics appeared to slow the development of uveitis in the mice and reduce the number of activated T cells. The researchers also found that microbe-rich extracts from model mouse intestines activated retina-specific T cells.

“It’s been known for other autoimmune diseases that gut bacteria can provide a necessary component, but the mechanism wasn’t known,” Caspi told The Scientist. “What appears to be happening is that they make some substance that, to the T-cells, looks like a protein from the retina.”

The researchers were unable, however, to identify the specific proteins or the bacteria that might produce this substance, which Caspi noted was a limitation of the study. It may be that a combination of bacteria work together to trigger the retina-specific T-cells, making the task of identifying the responsible proteins and bacteria even more challenging, she added.

The team was also unable to directly demonstrate that the retina-specific T helper cells in the gut are the same cells circulating to the eye—breaching the immune-privileged barrier to cause inflammation and disease, noted Veena Taneja, an immunologist at the Mayo Clinic in Rochester, Minnesota, who was not involved in the study. “They have not shown that these cells are the cells that cause disease,” she said. “And they have not shown that these cells are actually being activated in gut.”

Caspi said the team plans to continue to isolate the specific bacteria and/or proteins involved in activating the retina-specific T cells. “We don’t know what that actual protein is and I don’t know how long it will take to find it,” she said. “It may that we have to search far and wide for this mimic.”

R. Horai et al., “Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site,” Immunity,doi:10.1016/j.immuni.2015.07.014, 2015.

From Wiki:

Onset of uveitis can broadly be described as a failure of the ocular immune system and the disease results from inflammation and tissue destruction. Uveitis is driven by the Th17 T cell sub-population that bear T-cell receptors specific for proteins found in the eye.^[15] These are often not deleted centrally whether due to ocular antigen not being presented in the thymus (therefore not negatively selected) or a state of anergy is induced to prevent self targeting.^[16][17]

Autoreactive T cells must normally be held in check by the suppressive environment produced by microglia and dendritic cells in the eye.^[18] These cells produce large amounts of TGF beta and other suppressive cytokines, including IL-10, to prevent damage to the eye by reducing inflammation and causing T cells to differentiate to inducible T reg cells. Innate immune stimulation by bacteria and cellular stress is normally suppressed by myeloid suppression while inducible Treg cells prevent activation and clonal expansion of the autoreactive Th1 and Th17 cells that possess potential to cause damage to the eye.

Whether through infection or other causes, this balance can be upset and autoreactive T cells allowed to proliferate and migrate to the eye. Upon entry to the eye, these cells may be returned to an inducible Treg state by the presence of IL-10 and TGF-beta from microglia. Failure of this mechanism leads to neutrophil and otherleukocyte recruitment from the peripheral blood through IL-17 secretion. Tissue destruction is mediated by non-specific macrophage activation and the resulting cytokine cascades.^[19] Serum TNF-α is significantly elevated in cases while IL-6 and IL-8 are present in significantly higher quantities in the aqueous humour in patients with both quiescent and active uveitis.^[20] These are inflammatory markers that non-specifically activate local macrophages causing tissue damage.

Connie’s comments: Take your probiotic (acidophilus,yogurt,pickled veggies) and prebiotic (raw garlic, yellow foods) for the health of your gut and eyes.