At present, three major lines of thought prevail regarding the molecular mechanisms of immune privilege in the eye. First are the anatomic, cellular, and molecular barriers in the eye. Normal cornea lacks blood vessels and lymphatic vessels.
10 The central part of the cornea, which is used as donor tissue, contains only a small population of major histocompatability complex (MHC) class II–expressing antigen-presenting cells (APCs).
11 Although bone marrow–derived cells recently been reported to be present within normal cornea, most of these cells show an immature phenotype lacking MHC class II expression.
12 Moreover, normal corneal cells (i.e., epithelial, stromal, and endothelial cells) express no MHC class II and only weak MHC class I antigens.
13 –15 Second, anterior chamber-associated immune deviation (ACAID) is a well-known phenomenon in which antigen-specific peripheral tolerance is induced after antigen introduction into the anterior chamber.
16 The corneal graft necessarily forms the anterior surface of the anterior chamber, and donor-specific ACAID is induced after grafting.
17,18 Third, an immune-suppressive microenvironment is maintained in the eye. The anterior chamber contains biologically relevant concentrations of various immunomodulatory neuropeptides, growth factors, cytokines, and soluble cell-surface receptors, such as α-melanocyte-stimulating hormone,
19 vasoactive intestinal peptide,
20 calcitonin gene-related peptide,
21 transforming growth factor (TGF)-β,
22 thrombospondin-1,
23 macrophage migration inhibitory factor,
24 interleukin (IL)-1 receptor antagonist,
25 CD46,
26 CD55,
24 CD59,
24 and CD95L.
27 These factors suppress innate and adaptive immunity and maintain the immune suppressive microenvironment within the eye.
19 –27 In addition, normal corneal endothelial cells constitutively express immune-modulating factors such as CD95L
28 and B7-H1.
29 Corneal endothelium is thus considered to play a central role in the protection of corneal allografts from immunologic rejection when transplanted orthotopically into the eye
29,30 and heterotopically beneath the kidney capsule.
31,32 The molecular mechanisms underlying corneal invulnerability are not perfectly understood. Further investigations of the mechanisms of immune privilege are necessary for the development of new therapeutic approaches to prevent blinding inflammation within the eye and ameliorate the destructive inflammation observed in other tissues and organs.