Retinal Inflammation: Uveitis/Uveoretinitis

Retinal inflammatory disease of a putative autoimmune origin, known as autoimmune uveitis, affects 150,000 persons per year in the developed world and is a potentially blinding disease. The eye can be the only affected organ or uveitis can be part of a systemic syndrome. Animal models of uveitis induced by immunization with retinal antigens or through genetic engineering are used to study basic mechanisms, genetic control and therapeutic approaches. Although thymic expression of retinal antigens eliminates most autoreactive lymphocytes and positively selects natural regulatory T cells, peripheral tolerance to retina is inefficient due to the relative sequestration of retinal antigens. Therefore, residual autoreactive lymphocytes persist and can be activated by accidental encounter with self or a cross-reactive antigen. When exposed to retinal or cross-reactive antigens in the context of innate danger signals they mature into Th1 or Th17 effector cells that find their way into the eye. Upon recognition of specific antigen within the eye, they orchestrate a destructive inflammation by recruiting inflammatory leukocytes from the circulation. Regulatory T cells are also induced as part of the disease process and ultimately control inflammation and permit healing to take place. Novel immunotherapeutic approaches built upon the growing knowledge of basic mechanisms to target critical checkpoints in disease pathogenesis and restore immune homeostasis.