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Health See other Health Articles Title: Gut Microbes Activate T Cells Causing Autoimmune Eye Disease Medscape... NEW YORK (Reuters Health) - Commensal microbes in the gut can activate retina-specific T cells that go on to cause autoimmune uveitis in a mouse model, researchers report. "These findings allow us to understand the biological basis for the disease," lead author of the study, Dr. Rachel Caspi from National Eye Institute at the NIH in Bethesda, Maryland wrote via email to Reuters Health. "The findings should in no way be interpreted that a patient can pop a probiotic pill and their disease will improve, or that they should start taking antibiotics to eliminate commensal bacteria." In order to enter the eye, pathogenic T cells must first be activated, but the target antigens are sequestered in the eye and are not expressed in the periphery. A major unresolved question has been where such retina-specific T cells become activated. Knowing that T cells can be activated by microbial components in the gut environment, Dr. Caspi's team used the R161H mouse model of autoimmune uveitis to study natural triggers of the disease. They found that spontaneous uveitis in these mice is associated with enhancement of IL-17 producing T cells in the gut and that elimination of commensals not only attenuates uveitis but also reduces activation of those T cells in the intestine. Moreover, activation of these T cells is independent of endogenous interphotoreceptor retinoid-binding protein (IRBP) expression. Rather, the retina-specific T cells in the intestine are activated by signals derived from intestinal microbiota. Gut microbe-rich protein extracts contain all the stimuli needed to make retina-specific T cells capable of breaching the intact blood-retinal barrier and causing uveitis, according to the report published online August 18 in Immunity. "Our data uncover for the first time that lymphocytes which recognize self proteins (in our case retinal proteins) can be activated in the intestine through their specific receptors by the commensal bacteria to cause inflammation in the eye," Dr. Caspi said. "We believe that this could be an under-appreciated mechanism that might underlie other autoimmune diseases." SOURCE: http://bit.ly/1hrvzjH Immunity 2015. Poster Comment: Uveitis Definition Uveitis is an inflammation of the uveal tract, which lines the inside of the eye behind the cornea. Much of the uvea lies between the retina and tough, outer sclera. The uveal tract has three parts: the iris, the ciliary body, and the choroid. Uveitis is categorized according to the part of the uveal tract that is affected. Anterior uveitis is an inflammation of the front part of the uveal tract; it includes inflammation of the iris (iritis) and inflammation of the iris and the ciliary body (iridocyclitis). Posterior uveitis is an inflammation of the part of the uveal tract behind the lens of the eye. It includes inflammation of the choroid (choroiditis) and inflammation of the choroid and retina (chorioretinitis). Uveitis that affects the entire uveal tract is called panuveitis or diffuse uveitis. Description The uveal tract is made up of the iris, ciliary body, and choroid. The iris is the colored part of the eye. The ciliary body is inside the eye and produces a fluid called aqueous humor. Ciliary muscles aid in accommodation, the process of changing the shape of the lens in the eye to see things at various distances. The choroid lines the back of the eye and has many blood vessels. It helps nourish part of the retina. The choroid lies between the retina and outermost sclera. Uveitis may either persist for a long time (chronic) or have a short-term duration (acute). Anterior uveitis is classified as either granulomatous or nongranulomatous. The distinction is based on the disease agents that were considered responsible for the condition. At one time, it was thought that granulomatous uveitis was caused by tuberculosis bacilli whereas nongranulomatous uveitis was thought to be caused by streptococci. The distinction is still used even though the causes of uveitis are now understood differently. In most cases, uveitis affects only one eye, although posterior uveitis sometimes involves both eyes. About 60% of cases develop within the eye itself, but 40% are associated with systemic diseases or disorders ranging from toxoplasmosis to syphilis. Many of these are diseases of childhood and adolescence. Uveitis does not appear to run in families or to be associated with lifestyle choices, occupational history, geographical location, or environmental factors. Uveitis is a serious condition that may develop rapidly and cause lasting damage to the eye. Patients who think they may have chronic uveitis should seek evaluation and treatment by an ophthalmologist (a physician who specializes in diseases of the eye) as soon as possible. If the patient has a sudden loss of vision and the eye looks inflamed, the patient should go immediately to the doctor for emergency treatment. Causes and symptoms The causes of uveitis are not fully understood, but they can be a result of trauma, allergy, or a response to a systemic or ocular disease. Uveitis may be a type of immune-response mechanism. In people with impaired immune systems, uveitis may be due to an infection. Chronic uveitis is often associated with systemic disorders (e.g., Lyme disease, sarcoidosis, or juvenile rheumatoid arthritis). Anterior uveitis The so-called classic symptoms of anterior uveitis—severe pain; redness, particularly around the edge of the iris; and extreme sensitivity to light (photophobia)—occur mostly in acute uveitis. In anterior uveitis, the doctor will see a so-called "flare and cell" pattern when looking into the watery fluid (aqueous humor) between the cornea and the lens of the patient's eye. The iris may adhere to the lens, thus increasing the intraocular pressure. There may be nodules on the iris. There may be tearing and the pupil may be constricted and nonreactive. In severe cases of anterior uveitis, there may be hypopyon (a small amount of pus or collection of white cells) visible when the doctor examines the eye. GRANULOMATOUS UVEITIS. In granulomatous uveitis, there will be large yellowish-white cells visible on the back of the cornea, and possibly some small nodules on the iris. Granulomatous uveitis is usually less acute than the nongranulomatous form; the eye is only mildly inflamed and the patient's vision is somewhat blurred. Granulomatous uveitis can be produced by syphilis, toxoplasmosis, cytomegalovirus, sarcoidosis, tuberculosis, or Vogt-Koyonagi-Harada syndrome (VKH). VKH is marked by severe uveitis associated with hair loss, hearing loss, loss of pigment in the eyelashes and brows, and headaches. It occurs most commonly in Asians. NONGRANULOMATOUS UVEITIS. In nongranulomatous uveitis, the cells visible on the cornea are smaller, and there are no masses on the iris. This type of anterior uveitis is, however, more painful. The eye is red and the patient experiences both photophobia and loss of vision. Systemic diseases that can cause nongranulomatous uveitis include ankylosing spondylitis, Reiter's syndrome, psoriasis, ulcerative colitis, Behcet's syndrome, Lyme disease, and Crohn's disease. Children—especially girls—with anterior uveitis should be screened for juvenile rheumatoid arthritis (JRA). Posterior uveitis The symptoms of posterior uveitis are sometimes subtle. The patient may notice blurred or hazy vision, or floating black spots before the eyes. There may be pain and photophobia. The iris may attach to the lens in the eye thus increasing intraocular pressure. Posterior uveitis may be acute or chronic. It is more likely to involve both eyes. When the doctor examines the eye, cells may be seen in the vitreous humor, which is the normally transparent gel that fills the eyeball behind the lens. There will be yellowish or dark areas of inflammation on the choroid and the retina. The blood vessels in the retina develop a sheath or covering of inflammatory tissue. In severe cases, the vitreous humor is so cloudy that the doctor cannot see the retina at the back of the eye. PARS PLANITIS. Pars planitis is an inflammation of the pars plana, which is a part of the ciliary body. Pars planitis usually occurs in older children or young adults, and can develop into posterior uveitis. The diseases that cause granulomatous uveitis may also cause posterior uveitis. Diagnosis The eye doctor will examine the patient's eyes with a slit lamp in order to rule out conjunctivitis and certain types of glaucoma. The slit lamp is an instrument that combines a binocular microscope with a special light. The slit lamp can shine a narrow beam of very bright light into the eye and allow the doctor to examine the front part of the eye in detail. The slit-lamp exam is not painful, however if the patient is sensitive to light there will be discomfort. Post Comment Private Reply Ignore Thread
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