Innate and Adaptive Immunity of the Eye

Vision is of fundamental importance for each individual to interact with and to survive in the world. Therefore, a clear visual axis focusing the images from the world outside on retina, as well as a proper function of retina itself, is of paramount importance. In order to achieve this, clear media (cornea, aqueous humor (AqH), lens, and vitreous body) for transmission and focusing of the light is needed. The perception of precise images by the retina requires maintaining the organization and structure of retina within narrow limits. This organization can be disrupted by a potent inflammatory response that normally occurs in other sites in the body. Inflammation in the eye must therefore be very strictly regulated to avoid collateral damage to delicate structures lacking regenerative capacity. It has for many years been known that the eye is an immune privileged site (i.e., that allogeneic grafts placed in the anterior chamber or subretinally can survive for an extended period of time without being rejected). Medawar proposed immune privilege of the anterior chamber in the 1950s, observing this phenomenon by placing allogeneic skin transplants in the anterior chamber of the eye. He believed that the survival of the transplant was due to immunologic ignorance based on "passive" mechanisms, such as the blood:ocular barrier and the lack of lymphatics. This "dogma" prevailed until investigations initiated by Kaplan and Streilein (1977, 1978) 20 years later demonstrated that immunization via the anterior chamber created a deviant immune response (i.e., that F1 cells or allogeneic cells placed in the anterior chamber created a systemic immune response). This response was deficient in cell-mediated immunity and devoid of complement fixing antibodies. In the eye, the vitreous cavity and the subretinal space have also been found to be immune privileged areas (Jiang and Streilein, 1991; Wenkel et al., 1999). From the last decades of research it is now known that the immune privilege of the eye relies not only on passive mechanisms, such as the blood:ocular barrier and the lack of lymphatics, but also on active processes involving a complex array of different mechanisms. Other anatomic sites characterized as "immune privileged" include brain, testis, ovary, pregnant uterus, and adrenal cortex, where histoincompatible tissue grafts can be placed, and they survive for an extended or indefinite period of time (Streilein, 2003b). Tissues derived from immune privileged sites, such as the cornea, lens, retina, or retinal pigment epithelium (RPE) from the eye or tissues from the brain and spinal cord can, when placed at an immune competent site, survive without rejection for a prolonged period in a histoincompatible individual--a feature designating these tissues as "immune privileged tissues." This finding further indicates that the structural organization including blood:ocular or blood:brain barriers of the "immune privileged sites" is not the full explanation of this phenomenon. Today the "immune privileged" status of the eye is believed to be based on five different mechanisms including: (1) the blood:ocular barrier, (2) the absence of lymphatic drainage from the eye, (3) soluble factors with immune regulatory properties in ocular fluids, (4) the expression of immune regulatory molecules on the epithelial cells lining the interior of the eye, and (5) tolerance-inducing antigen presenting cells (APC). Some of these mechanisms will be described in the following sections (Table 1).