The immune system doesn't know that your eye's exist - Ocular immune privilege

[zaax]

ncbi.nlm.nih.gov/pmc/articl....

The eye has a special relationship with the immune system, known as immune privilege. The term was coined in the 1940s by Sir Peter Medawar, who noticed that foreign tissue grafts placed in the anterior chamber (AC) of the eye were not rejected [1]. While the concept of immune privilege is simple, research into its nature has revealed its highly complex character, which is still incompletely understood (reviewed in [2]). Multiple mechanisms combine to maintain immune privilege:

(a) Physical barriers (efficient blood-retina barrier and lack of efferent lymphatics) prevent free entry and exit of cells, and even larger molecules, into and out of the eye. The integrity of the blood-retinal barrier is routinely measured in the clinic by the fluorescein test and provides a widely accepted measure of ocular health. Nevertheless, the concept of sequestration of the eye from the immune system has recently been debated, mostly on the basis of the phenomenon known as anterior chamber-associated immune deviation (ACAID). (See item (c) below.)

(b) The inhibitory ocular microenvironment, composed of cell-bound and soluble immunosuppressive factors within the eye, inhibits the activity of immune-competent cells. The soluble factors include transforming growth factor-beta (TGF-β) (which can also be membrane-bound), neuropeptides such as alpha-melanocyte-stimulating hormone (α-MSH), vasoactive intestinal peptide, and others. Ocular resident cells directly inhibit immune cells (at least in culture) by secreting soluble factors and by contact-dependent mechanisms. Retinal glial Müller cells were the first to be identified, but their inhibitory surface molecules were not characterized [3]. The pigmented epithelia of the retina (RPE) and the iris/ciliary body (IPE) not only inhibit T cells, but also induce them to become T regulatory (Treg) cells [4]. Surface-bound molecules involved in these processes include CD86 [which engages cytotoxic T lymphocyte antigen 4 (CTLA-4) on T cells], FasL, thrombospondin, and galectins [4,5].

(c) Finally, the eye actively regulates systemic immune responses. The classic example is ACAID, a unique and highly orchestrated immune response to antigens injected into the AC. It involves migration from the eye to the spleen of F4/80+ antigen-presenting cells that interact with invariant natural killer T cells and B cells and culminates in elicitation of systemic regulatory immunity through induction of CD4+ afferent and CD8+ efferent Treg cells (reviewed in [4,6]). Proteins and even cells or cellular fragments were shown to pass from the AC directly into the blood through a highly porous structure known as the trabecular meshwork. While some regard this as negating the concept of ocular antigen sequestration, elicitation of ACAID requires puncturing of the eye with a needle and perturbation of ocular integrity. It is therefore likely that ACAID is more representative of a response to trauma rather than of a mechanism of tolerance to tissue-specific antigens contained in the healthy eye. A less controversial example is post-recovery tolerance, in which spleen cells from mice that have recovered from experimental autoimmune uveitis (EAU) contain regulatory activity, whose generation is dependent on the presence of eye [7-9]. This type of tolerance was shown to involve the melanocortin pathway and cannot be induced in melanocortin-5 receptor knockout mouse, but whether it is α-MSH from the eye that is involved has not been determined.

A highly successful application of the ocular immune privilege is corneal transplantation. Corneal allografts are up to 90% successful without tissue matching and without systemic immunosuppressive therapy [10]. On the downside, however, ocular immune privilege may leave the eye vulnerable to autoimmunity by impeding peripheral tolerance to eye-specific antigens sequestered behind the blood-retinal barrier [8].

Continued at@ ncbi.nlm.nih.gov/pmc/articl....

[Shepherd777]

I never thought about why corneal transplants did not require a patient to take medication that kept the body from rejecting the transplants. Very interesting when other body parts from others look for blood type and other genetic info for a close match.

[Smakwater]

The eye is beyond fascinating. The eye also communicates light measurements to the pineal gland to influence regulated neurotransmission.

At times I experience an abnormal reuptake condition due to a torn pineal gland from a previous surgery. It can be very interesting at times to recognize and cognitively discipline ones demeanor during a hyper secretion or suppressed neurotransmission event.

JM