Autoimmune Disease Behind Blindness Caused By Gut Microbes

Autoimmune uveitis is among the leading causes of blindness. There exist microbes that dwell naturally in our intestines that can be trigger to this disease, and a new study has found that some such microbes produce proteins that candor to harmfully maladjusted immune cells’ entering our eyes.


This notion of intestinal microbes promoting autoimmune uveitis “has been there in the back of our minds,” comments ocular immunologist Andrew Taylor of the Boston University School of Medicine, a scientific bystander. “This is the first time that it’s been shown that gut flora seems to be part of the process.”

In fact, roughly 400,000 people presently in the States have autoimmune uveitis, a disease that sets the body’s means of controlling the immune system, T cells, on a mission to invade the eye and damage its middle layer. T cells are triggered by a special molecule called antigens, and when eye proteins are misidentified as antigens, T cells go haywire and attack. This isn’t an exceptional condition; healthy people possess the same T cells, it’s just that they don’t usually attack the eyes en masse. In order for T cells to attack at all they must first be activated by their corresponding antigen. It’s rare for antigens associated with autoimmune uveitis to leave the eye, so the question at hand is how on Earth are the wrong T cells stimulated the wrong way?


The new study’s immunologist Rachel Caspi of the National Eye Institute in Bethesda, Maryland, along with her colleagues, performed some genetic engineering on mice to trigger their T cells in the wrong way described above. The critters developed symptoms just as they were weaned. However, the study found that giving the mice four antibiotics capable of killing most of their gut microbes actually delayed the onset and reduced the severity of the disease. This effect was also noticed in germ-free mice, referred to as such because of their lack of gut bacteria.


In order to know if gut microbes were actually stimulating the wrong T cells, Caspi and crew mixed intestinal contents of diseased mice to T cell cultures. This lovely cocktail activated the T cells, which means they had become the wrong kind, ready to infect. Caspi’s team suspected a specific protein intestinal microbes release of triggering T cells, so they injected a protein-destroying enzyme to the intestinal cocktail. Afterwards the T cell had a sluggish response to stimuli, which lends weight to the notion of them responding to a protein. Separately, scientists injected T cells from genetically altered mice into control mice not susceptible to autoimmune uveitis, the hypothesis being that T cells unexposed to intestinal material cannot cause uveitis. However, 86% of the mice developed the disease unless they had not received the major dose of T cells formerly exposed to diseased intestinal contents, reported researchers in Immunity, yesterday.

This means that a specific group of bacteria natural to the intestines produces proteins akin to those found in the eye, activating T cells present in the intestines. “We can prove that activation is occurring in the gut,” Caspi announced. Post-activation, these renegade T cells are then presumed to journey up to the eyes, where they force their way in and wreak a blinding havoc.
“It’s a very rigorous approach, and it really adds to our knowledge” regarding how autoimmune uveitis gets its start, remarked ocular immunologist Russell Read of the University of Alabama, Birmingham, another scientific spectator.


So far this is solid scientific progress, but the next question to answer, according to immunologist James Rosenbaum of the Oregon Health & Science University in Portland, is why only some (and not all) of us develop autoimmune reactions in our retinas. He goes on to suggest that perhaps only some humans have the bacteria necessary to stimulate T cells, or that a genetic predisposition may be involved.

Caspi and crew don’t want to raise false hopes of popping some antibiotic to cure autoimmune uveitis, but by cataloging gut mimesis of ocular proteins in conjunction with trigger-happy bacteria, researchers may one day procure new methods to treat or prevent this mysterious disease.

story originally covered by Mitch Leslie of Science Magazine