Features of the Immunologic Microenvironment
The anterior chamber is a fluid-filled cavity; circulating aqueous humor provides a unique medium for intercellular communication among cytokines, immune cells, and resident tissue cells of the iris, ciliary body, and corneal endothelium. Although aqueous humor is relatively protein depleted compared with serum (containing about 0.1%–1.0% of the total serum protein concentration), even normal aqueous humor contains a complex mixture of biological factors, such as immunomodulatory cytokines, neuropeptides, and complement inhibitors that influence immunologic events within the eye.
A partial blood–ocular barrier is present. Fenestrated capillaries in the ciliary body allow a size-dependent concentration gradient of plasma macromolecules to permeate the interstitial tissue. Smaller plasma-derived molecules are present in higher concentration than larger molecules. The tight junctions between the pigmented and nonpigmented ciliary epithelium provide a more exclusive barrier, preventing interstitial macromolecules from permeating directly through the ciliary body into the aqueous humor. Nevertheless, a small number of plasma macromolecules bypass the nonpigmented epithelium barrier. They can permeate by diffusion anteriorly through the uvea to enter the anterior chamber through the anterior iris surface.
Few resident T lymphocytes and some mast cells are present in the normal anterior uvea. B lymphocytes, eosinophils, and neutrophils are normally not present. Very low concentrations of IgG and complement components occur in normal aqueous humor. The iris and ciliary body contain significant numbers of macrophages and dendritic cells that serve as APCs and possible effector cells. Immune processing is unlikely to occur locally. Rather, because the inner eye does not contain well-defined lymphatic channels, clearance of soluble substances depends on aqueous humor outflow channels; clearance of particulates depends on endocytosis by trabecular meshwork endothelial cells or macrophages. Nevertheless, antigen inoculation into the anterior chamber results in efficient communication with the systemic immune response. Intact soluble antigens gain entrance to the venous circulation, through which they are transported to the spleen.
The vitreous has not been studied as extensively as the anterior chamber. Studies employing proteomics reveal the vitreous as a physiologically active, complex tissue containing diverse proteins originating from inside and outside the eye. An important source for these inflammatory mediators is the retina. The vitreous gel can also electrostatically bind charged protein substances and can serve as an antigen depot as well as a substrate for leukocyte cell adhesion. Hyalocytes are modified resident macrophages. They are important in vitreal immunoregulation/modulation and frequently act as antigen-presenting cells. They also respond to different cytokines, playing a role in the immunopathogenesis of several disorders, including proliferative vitreoretinopathy (PVR). Because the vitreous contains collagen type II, it may also serve as a depot of potential autoantigen.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.