The double-edged ocular immune response: the Cogan lecture.

The immune system has evolved to protect the body against infectious microbes and toxic insults. To achieve this mission, the immune system contains a plethora of well-choreographed defense mechanisms. Cells of the immune system, such as specific killer T cells, natural killer cells, polymorphonuclear leukocytes, and macrophages, directly attack pathogens. Cells involved in humoral and cellular immunity produce additional mediators of immune protection, including antibodies, cytokines, chemokines, and complement, to aid in the war against foreign invaders. Although the induced inflammatory response protects tissues against these insults, the inflammation can itself induce tissue damage and functional disruption as a result of necrosis and fibrosis. This article will illustrate how the immune response can act as a double-edged sword, both protecting and damaging the host. The first part of the article will show how even small amounts of inflammation in the eye can impair vision and discusses how advances in our understanding of ocular immunology have allowed development of improved therapies for inflammatory eye diseases such as uveitis. The second discusses cytomegalovirus (CMV) retinitis, a blinding complication of severely immunosuppressed patients. The history of this disorder in patients with the acquired immunodeficiency syndrome, before and after the development of highly active antiretroviral therapy (HAART) will illustrate that, despite the problems of ocular inflammation, the eye is far better off with a healthy immune response.