[Show abstract][Hide abstract] ABSTRACT: Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate the immune privileged mechanism called anterior chamber-associated immune deviation (ACAID). Previously, we showed that retinal laser burn (RLB) to one eye abrogated immune privilege (ACAID) bilaterally for an extended period of time. In an effort to explain the inflammation in the nonburned eye, we postulated that neuronal signals initiated inflammation in the contralateral eye. In this study, we test the role of substance P, a neuroinflamatory peptide, in RLB-induced loss of ACAID. Histological examination of the retina with and without RLB revealed an increase of the substance P-inducible neurokinin 1 receptor (NK1-R) in the retina of first, the burned eye, and then the contralateral eye. Specific antagonists for NK1-R, given locally with Ag within 24 h, but not 3, 5, or 7 d post-RLB treatment, prevented the bilateral loss of ACAID. Substance P knockout (KO) mice retained their ability to develop ACAID post-RLB. These data support the postulate that substance P transmits early inflammatory signals from the RLB eye to the contralateral eye to induce changes to ocular immune privilege and has a central role in the bilateral loss of ACAID. The possibility is raised that blocking of the substance P pathway with NK1-R antagonists postocular trauma may prevent unwanted and perhaps extended consequences of trauma-induced inflammation in the eye.
Preview · Article · Jun 2012 · The Journal of Immunology
[Show abstract][Hide abstract] ABSTRACT: Immune privileged mechanisms allow the eye to be protected from the pathological consequences of inflammation by expressing immune responses that do not elicit inflammation. These mechanisms are established with rigor and very few experimental events have been capable of aborting immune privilege in the ocular environment. The multiple overlapping mechanisms that contribute to the totality of ocular immune privilege are reviewed here, in the light of contemporary knowledge of immune homeostasis throughout the organisms. The review considers the regulatory mechanisms in terms of 1) physical and structural barriers that lessen the availability of immune cells to reach the eye; 2) activities that prevent the immune response from being activated in the ocular tissue; 3) events that actively induce apoptosis or anergy of the immune cells; 4) the protective system of the pigmented cells that line the border of the eye and prevent immune activation or actually modulate the function of the activated immune cells; and 5) mechanisms of anterior chamber immune deviation, ACAID, a paradigm of mechanisms that induces Treg cells in the periphery to seed the local area and is proposed to contribute to self tolerance of ocular antigens. The consequences of losing immune privilege are considered.
No preview · Article · Aug 2011 · Current Immunology Reviews
[Show abstract][Hide abstract] ABSTRACT: Immune privilege allows for the immune protection of the eye in the absence of inflammation. Very few events are capable of overcoming the immune-privileged mechanisms in the eye. In this study, we report that retinal laser burn (RLB) abrogates immune privilege in both the burned and nonburned eye. As early as 6 hours after RLB, and as late as 56 days after RLB, antigen inoculation into the anterior chamber of the burned eye failed to induce peripheral tolerance. After RLB, aqueous humor samples harvested from nontreated eyes but not from either the burned or the contralateral eye, down-regulated the expression of CD40 and up-regulated interleukin-10 mRNA in peritoneal exudate cells, and converted peritoneal exudate cells into tolerogenic antigen-presenting cells (APCs). Unlike F4/80(+) APCs from nontreated mice, F4/80(+) APCs from RLB mice were unable to transfer tolerance after anterior chamber inoculation of antigen into naïve mice. The increased use of lasers in both the industrial and medical fields raises the risk of RLB-associated loss of immune regulation and an increased risk of immune inflammation in the eye.
Preview · Article · Feb 2009 · American Journal Of Pathology