The eye as a privileged organ: aspects of corneal transplantation

The human eye has immunological peculiarities. The graft rejection rate, for example, is just 10%. For non-vascularised corneas only about 2%.

The immune privilege of the eye

There are hardly any phagocytic antigen-presenting cells or lymphoid structures in the eye. The expression of MHC-I and II molecules is also clearly limited. In the central corneal epithelium, even certain immune cells (Langerhans cells) are completely absent. The removal of antigens therefore takes place via the trabecular meshwork. In addition, there are the blood-aqueous humor and blood-retina barriers. The latter two also ensure that the refractive properties of aqueous humour and vitreous fluid are maintained. If an ocular immune response occurs, there are some specific features of the afferent and efferent phases.1-3

Limited regenerative capacity of neuronal structures

Mother nature has ensured that there is a physiologically-reduced response of the ocular immune system. There is a reason for this: We know that neuronal structures (optic nerve head and retina) are hardly capable of regeneration. An immune response in the eye would have devastating consequences. Scarring in the area of the optic axis would also be accompanied by a significant reduction in visual acuity.1-3

The eye is not alone

The eye is not the only organ that has immune privilege. The brain, liver, adrenal glands, ovaries and testes are also involved. Organs with limited regenerative capacity rely on their immune privilege. But how exactly does immune privilege work at the cellular level?1-3

No classical immune response

Three crucial factors characterise the immune privilege of the eye: separation, suppression and regulation. Separation from the components of the blood circulation occurs through the blood-eye barriers. Normally, the cornea and anterior chamber of the eye are avascular.1-3

Resistance is futile

If activated lymphocytes manage to pass through the barriers of the eye, an immunomodulatory process intervenes. The aqueous humour itself contains immunomodulatory factors (TGF-β, α-melanocyte stimulating hormone and anticomplimentary factors) and certain ligands (Qa-1, Fas ligand and indoleamine 2,3-dioxygenase) are also found on the surfaces of the cells or in the tissue. These have an immunosuppressive effect on the newcomer.4

ACAID (anterior chamber-associated aberrant immune response) - the slightly different immune response

If an antigen enters the anterior chamber of the eye, a delayed antigen-specific hypersensitivity response occurs. All in all, an antigen in the eye is in a rather immunosuppressive environment. It is therefore not surprising that antigen injection into the anterior chamber can lead to systemic suppression of the cell-mediated immune response and the formation of complement-binding IgG antibodies.4

  1. Stein-Streilein J. et al. (2014). Immune Privilege and the Philosophy of Immunology. Front Immunol. 2014; 5: 110.
  2. Louveau A. et al. (2015).Revisiting the concept of CNS immune privilege. Trends Immunol. 2015 Oct; 36(10): 569–577.
  3. Taylor A.W. et al. (2016). Ocular Immune Privilege and Transplantation. Front Immunol. 2016; 7: 37.
  4. Cone R. E. et al. (2009). Anterior Chamber-Associated Immune Deviation (ACAID): An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage? Ophthalmol Eye Dis. 2009; 1: 33–40.