Macrophages and Uveitis in Experimental Animal Models

Abstract

Resident and infiltrated macrophages play relevant roles in uveitis as effectors of innate immunity and inductors of acquired immunity. They are major effectors of tissue damage in uveitis and are also considered to be potent antigen-presenting cells. In the last few years, experimental animal models of uveitis have enabled us to enhance our understanding of the leading role of macrophages in eye inflammation processes, including macrophage polarization in experimental autoimmune uveoretinitis and the major role of Toll-like receptor 4 in endotoxin-induced uveitis. This improved knowledge should guide advantageous iterative research to establish mechanisms and possible therapeutic targets for human uveitis resolution.

New Immunosuppressive Therapies in Uveitis Treatment

“…To achieve it, the eye has anatomical mechanisms, like a physical barrier called the hemato-retinal barrier and lack of lymphatic drainage, and also molecular mechanisms, such as secretion of soluble immunosuppressive factors by eye cells, such as β-TGF, Fas ligand (FasL) or the low expression of MHC class II molecules in antigen-presenting cells [ 11 ]. These mechanisms also help inactivate the immune response of pigment epithelium cells with similar characteristics to macrophages, which are capable of secreting anti-inflammatory cytokines and Müller cells, and have been shown to inhibit the proliferative capacity of T-cells in cultures [ 11 , 12 ].…”

“…Thus the location of alloantigens in the anterior chamber brings about a form of immune tolerance identified as anterior chamber-associated immune deviation (ACAID), which induces antigen-specific CD8 + Tregs and contributes to the eye’s immune privilege by down-regulating immune responses. Treg cells avoid autoimmune diseases by upholding self-tolerance and defeating pathogen-induced immunopathology [ 12 ].…”

“…Since the 1980s, the T helper cell types 1 and 2 (Th1 and Th2) paradigm has been considered the cornerstone of immune responses. Th1 cells, which secrete IL-2, INF-γ, and lymphotoxin, are critical for macrophage activation and nitric oxide production [ 12 ]. Th2 cells, which secrete IL-4, IL-5 and IL-13, mediate for humoural immune responses.…”

“… Uveitis results from imbalance between inflammatory mechanisms and regulatory mechanisms. Acute inflammation initiated by those cells that are previously present in affected tissues, mainly resident macrophages and dendritic cells [ 12 ]. In autoimmune uveitis, self-reactive T cells leave the thymus and when they reach the eye they come in contact with retinal antigens.…”

Modern Opportunities in Uveitis Treatment

“…Такой антиген индуцирует антигенспецифические Т-регуляторные клетки и способствует поддержанию иммунной привилегии глаза посредством подавления иммунного ответа. Регуляторные Т-клетки предотвра-щают аутоиммунные заболевания, поддерживая ауто-толерантность и предотвращая сдвиги иммунитета, вы-званные патогенами [7].…”