Researchers from L V Prasad Eye Institute have for the first time found evidence of how TB infection of the eye leads to autoimmunity causing widespread disease of the eye (uveitis). TB infection damages the blood-retinal barrier allowing blood to reach the retina. Once inside the eye, autoimmune cells specifically target the retina where they proliferate and produce cytokines leading to uveitis.
Researchers from Bhubaneswar have for the first time found evidence of how TB infection of the eye leads to autoimmunity — wherein the immune cells attack the cells of the body instead of protecting them — causing widespread disease of the eye (uveitis). According to the NIH’s National Eye Institute, U.S., uveitis is a group of inflammatory diseases that produces swelling and destroys eye tissues. Uveitis can cause mild to severe vision loss.
“TB-associated uveitis is the most common cause of infectious uveitis in India. It causes about 10% of all infectious uveitis,” says Dr. Soumyava Basu from L V Prasad Eye Institute, Bhubaneswar.
Certain parts of the body such as the eye, brain, and reproductive organs (testes and uterus during the time of pregnancy) are immune-previleged, in that they effectively prevent the entry and exit of cells, the immune cells included. In the case of the eye, the blood-retinal barrier does the job of blocking the entry of immune cells. The immune privilege of the eye is exploited for corneal transplantation from cadavers without the need for tissue matching, unlike in the case of other organs such as kidney.
“It’s generally believed that infection and autoimmunity are two separate entities and follow different paths during the evolution of disease. But we found TB infection of the eye was responsible for the activation of autoimmunity,” says Dr. Basu who is one of the corresponding authors of a paper published in the journal Investigative Ophthalmology & Visual Science. The work was done in collaboration with Dr. Satish Devadas from the Institute of Life Sciences, Bhubaneswar.
The TB infection of the eye per se does not cause autoimmunity. Instead, it is likely that TB infection damages the blood-retinal barrier thereby allowing some of the autoimmune cells that are present in the blood to reach the retina. Once inside the eye, the autoimmune cells specifically target the retina where they proliferate in large numbers and produce inflammatory chemicals called cytokines, leading to widespread eye disease.
“T cells are generated in the thymus and get exposed to different cell types present in the body. While most T cells that act against body cells (autoimmunity) naturally die in the thymus, a few escape and enter the blood circulation,” says Ravichandra Tagirasa who is first author of the paper.
The researchers isolated vitreous humor (gel) from the diseased eye of patients with ocular TB and stimulated the immune cells using either TB antigen or retinal antigen. “We thought only the TB antigen can activate the T cells. But to our surprise, both antigens were able to activate the T cells. This was completely unexpected,” says Tagirasa.
Though both TB-specific and retinal-specific immune cells are present in the eye, the researchers found only the retinal-specific immune cells were responsible for the inflammation and eye disease.
In subsequent experiments, the researchers found retinal-specific immune cells (T cells) were also resistant to cell death. While the TB-specific T cells were dying at a normal rate, retinal-specific autoimmune T cells that were activated weren’t dying easily in the eyes. The ability of the retinal-specific autoimmune cells to persist in the eye for longer duration results in persistent inflammation and prolongation of the disease process. This adversely affects the long-term prospects for restoring good vision in the affected eyes.
“As there are many retinal-specific T cells, prescribing only anti-TB drugs is not enough. The patients must be given adequate anti-inflammatory therapy as well,” says Dr. Basu.