oa Editorial [Hot topic: Ocular Immunology (Guest Editor: Gerhild Wildner)]

Ocular Immunology is a growing field in the last years. For a long time the eye was regarded as a “protuberance” of the brain, but now many special characteristics different from the brain and other regions of the body have been identified. The inner eye is “immune privileged”, which prevents spontaneous assaults from the immune system and rather induces immune tolerance than defense. The external surfaces of the eye have to deal with the environment, which includes harmless antigens as well as pathogens. Those pathogens that can cause tremendous problems to the surface (cornea) as well as in the inner eye are herpes viruses, which commit a life-long relationship with their host. Herpes keratitis and HSV uveitis are sight-threatening diseases, which are caused by the viruses themselves and, on the other side, by the host's own immune system. The characteristics of the infection by various herpes viruses as well as the immune reaction of the host is extensively reviewed by G.M.G.M Verjans and A. Heiligenhaus (Herpes Simplex Virus-induced ocular diseases - Detrimental interactions between virus and host) in this issue. Herpes keratitis can blur the corneal stroma to an extent that needs corneal transplantation. The normally clear cornea allows the light to pass through and reach the retina for photoperception, and enables us to directly observe the intraocular tissues and inflammatory events. The cornea is a part of the anterior chamber-associated immune privilege, which confers long-term acceptance of corneal grafts under non-inflamed conditions. The latter is, however, abolished after herpes infection. J.Y. Niederkorn describes in his review “Cornea: Window to ocular immunology” how and why the cornea is involved in the immune privilege and what happens when the immune privilege breaks down. In addition to the capabilities of the cornea to protect itself against infection and contribute to the immune privilege of the anterior chamber, the author also covers the immune principles of dry eye disease. The immune privilege of the eye has been a topic of intensive research in the past decades, for it protects the delicate intraocular tissues from irreversible damage by the immune system. Not only the anterior chamber, but also the retina is concerned about its integrity and is thus provided with mechanisms to downregulate potentially deteriorating immune responses, as described by J. Stein-Streilein and K. Lucas in their article “A current understanding of ocular immune privilege”. Each eye takes care of the other, that is, the generation of regulatory T cells that confer tolerance will also protect the contralateral eye from deleterious immune responses. On the other hand, this group has recently show that loss of ACAID in one eye leads to loss of protection in the contralateral eye as well, an effect that could be attributed to neuropeptide mediators. S.W. McPherson and his colleagues N.D. Heuss, U. Lehmann and D.S. Gregerson focus on the “Generation of regulatory T cells to antigen expressed in the retina”, and they describe that regulatory T cells specific for sequestered retinal antigens can be generated from mature, peripheral T cells. Their transgenic mouse model enabled the authors to dissect the generation of regulatory T cells by ectopic expression of antigen in the thymus from the generation of Tregs by antigen expressed exclusively in the retina. These cells are able to protect from experimental autoimmune disease directed against the retina. Despite of the necessity for preventing the eye from immune assault, it is sometimes essential for the immune system to be active within the eye, especially when pathogens have invaded. This will lead to a breakdown of the blood-ocular barriers and the tolerance that is usually established by ACAID. Innate as well as adaptive immune responses can result in sight-threatening conditions. In their article “Intraocular immune reactions during uveitis” J. Curnow, G. Wallace, A. Denniston and P. Murray focus on human disease. They cover the different immune reactions in autoimmunity and autoinflammation, the role of genetic factors such as HLA-associations, cytokines and chemokines that are related to different types of uveitis, and finally dwell on the mechanisms underlying the current therapies....