Development of a cell therapy treatment for uveitis

Uveitis describes inflammation within the eye (intraocular inflammation) and is sight-threatening, particularly when it affects the retina (uveoretinitis), the sight-generating “nerve-layer” of the eye.

Treatment of uveitis relies heavily on the use of systemic steroids and other relatively non-specific immunosuppressants, which have serious and sometimes life-threatening side effects.

Many cases of uveitis are initiated by infection but in about half of the cases, no direct infectious cause can be found. However, in both categories of uveitis (infection or no infection), the patient’s immune system goes into overdrive and much of the damage is actually caused by over-reacting immune cells, produced by the patient, which attack the retina. In fact, such cells are constantly produced in everyone, but in healthy individuals they are kept under control by Tregs (the “T” signifying they are produced in the primary immune organ, the thymus).

However, in many diseases, the number or quality of Tregs is reduced and unrestrained over-reacting immune cells (cytotoxic cells) are set free to cause damage. Cytotoxic cells are produced whenever we are attacked by infection and are necessary to clear the infectious agent, but once the infection is cleared, Tregs keep the cytotoxic cells in check, and prevent them from causing damage to healthy tissues (bystander damage). Accordingly, when Tregs are lacking or non-functional, a post-infectious inflammation continues and in cases of uveitis a failure of Tregs to control damaging over-reacting cells, of unknown provenance, still underlies the sight-threatening uveitis.

Researchers aim to provide pre-clinical evidence for an alternative approach to treatment of uveitis, namely patient-specific, “customised cell therapy in which the cells causing damage to the eye are suppressed by transfusion of “regulator” cells (Tregs) from the patient’s own immune system.