The sequence of events in EAU appears to be focal adhesion of leukocytes to discrete sites on postcapillary venules, followed by upregulation of adhesion molecules, especially ICAM-1 and P-selectin, and breakdown of the BRB, leading to transendothelial migration of leukocytes and recruitment of large numbers of cells to the retinal parenchyma. These changes occur over a short period of 6 to 9 days pi and initiate the process of tissue damage during the following 2 to 3 weeks.
A novel population of 33D1(+) DCs was identified in normal mouse retina. The function of these cells remains to be defined, but increased numbers correlate positively with structural abnormalities in the RPE and increased resistance of the strain to EAU.
Immune-mediated inflammation in the retina is regulated by a combination of anatomical, physiological and immuno-regulatory mechanisms, referred to as the blood-retina barrier (BRB). The BRB is thought to be part of the specialised ocular microenvironment that confers protection or "immune privilege" by deviating or suppressing destructive inflammation. The barrier between the blood circulation and the retina is maintained at two separate anatomical sites. These are the endothelial cells of the inner retinal vasculature and the retinal pigment epithelial cells on Bruch's membrane between the fenestrated choroidal vessels and the outer retina. The structure and regulation of the tight junctions forming the physical barrier are described. For leukocyte migration across the BRB to occur, changes are needed in both the leukocytes themselves and the cells forming the barrier. We review how the blood-retina barrier is compromised in various inflammatory diseases and discuss the mechanisms controlling leukocyte subset migration into the retina in uveoretinitis in more detail. In particular, we examine the relative roles of selectins and integrins in leukocyte interactions with the vascular endothelium and the pivotal role of chemokines in selective recruitment of leukocyte subsets, triggering adhesion, diapedesis and migration of inflammatory cells into the retinal tissue.
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