Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation

Abstract

The delicate visual axis that makes precise vision possible is highly vulnerable to the destructive potential of immunogenic inflammation. Immune privilege of the eye is the experimental expression of the way in which evolution has coped with the countermanding threats to vision of ocular infections and ocular immunity and inflammation. Ocular immune privilege has five primary features that account for its existence: blood:ocular barriers, absent lymphatic drainage pathways, soluble immunomodulatory factors in aqueous humor, immunomodulatory ligands on the surface of ocular parenchymal cells, and indigenous, tolerance-promoting antigen-presenting cells (APCs). Three manifestations of ocular immune privilege that have received the most extensive study are the intraocular microenvironment, which is selectively anti-inflammatory and immunosuppressive; the prolonged acceptance of solid tissue and tumor allografts in the anterior chamber; and the induction of systemic tolerance to eye-derived antigens. Anterior chamber-associated immune deviation is known to arise when indigenous, ocular APCs capture eye-derived antigens and deliver them to the spleen where multicellular clusters of these cells, natural killer T cells, marginal zone B cells, and gammadelta T cells create an antigen-presentation environment that leads to CD4(+) and CD8(+) alpha/beta T cells, which as regulators, suppress induction and expression of T helper cell type 1 (Th1) and Th2 immune expression systems. The ways the eye influences local and systemic immune responses to ocular antigens and pathogens carry risks to and benefits for mammalian organisms. As loss of sight is a powerful, negative-selecting force, the benefits of ocular immune privilege outweigh the risks.

Implanted islets in the anterior chamber of the eye are prone to autoimmune attack in a mouse model of diabetes

“…However, under some circumstances ocular immune privilege is lost (e.g. allogeneic cornea grafts are no longer protected from immune rejection [30]). The current study and that of Abdulreda et al [18] support the notion that pancreatic islets are not protected from autoimmune processes when transplanted into the anterior chamber.…”

OVA-specific CD8+T cells do not express granzyme B during anterior chamber associated immune deviation

“…Their role in ACAID, a deviant immune response elicited by intracameral injection of antigen, has however not been well addressed. ACAID is characterized by a deficiency in delayed-type hypersensitivity (DTH) responses and decreased expression of IgG isotypes [24,28]. Furthermore, allogeneic tumor cells injected into the AC grow progressively, whereas these cells do not expand when injected elsewhere in the body [26].…”

The immunomodulating neuropeptide alpha-melanocyte-stimulating hormone (α-MSH) suppresses LPS-stimulated TLR4 with IRAK-M in macrophages

“…This regional immunity was first experimentally observed by Medawar and his colleagues in the 1940s where they describe the prolong survival of incompatible grafts placed into the anterior chamber of the eye (Medawar, 1948). This immunosuppression is considered an evolutionary adaptation to prevent vision loss caused by the irreversible collateral tissue damage of autoimmune disease and delayed-type hypersensitivity (Streilein, 2003). The unique regulation of immunity in the eye is mediated in part by factors produced and expressed within the ocular microenvironment.…”