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. 2022 Sep 9;13:983964. doi: 10.3389/fimmu.2022.983964

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Copyright © 2022 Opdenakker, Vermeire and Abu El-Asrar

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Comparison of intestinal with blood-retinal barrier. Panel (A): The barrier of the intestinal epithelium protects the underlying tissue against invasion of microorganisms and diffusion of detrimental microbial molecules from within the lumen, while functioning mainly as area of transport of nutrients and fluid (large grey arrow on the background) into the subepithelial blood vessels (in red). The intestinal barrier is composed of tight junctions (indicated by two short black lines at the luminal side) between the epithelial cells (shown in blue) and by a basement membrane (indicated by the continuous subepithelial black line at the basolateral side). In addition, a mucus layer (in orange) produced by goblet cells (not shown) forms further protection against bacterial infection. In IBD, the pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) induce locally the production of interleukin-8 (IL-8/CXCL8). IL-8 chemo-attracts neutrophils form capillaries and activates these cells to degranulate, yielding proteolysis by matrix metalloproteinases (MMPs), unencumbered by TIMP-1. Neutrophil collagenase/MMP-8 and gelatinase B/MMP-9 not only break down basement membrane collagens, but they also cleave the tight junction claudins and occludins. Neutrophils also produce calprotectin and neutrophil gelatinase B-associated lipocalin (NGAL) and covalent complexes with MMP-9 (MMP-9/NGAL). When the intestinal barrier is broken in the pathological conditions of IBD, neutrophil products may end up in the lumen and these may be detected in the faeces as IBD biomarkers. In Panel (B), a comparison is made with the more complex barriers in the retina. The retina uses blood supply from two sources and, consequently, has two blood-retinal barriers (BRB). The inner retina derives blood from the retinal circulation (large grey arrow on the left side). The inner BRB is produced by the tight junctions between endothelial cells of the retinal circulation. The outer retina is supplied with blood from the choroidal circulation (bidirectional large grey arrow on the right side). The outer BRB is established by the tight junctions of the retinal pigment epithelial (RPE) cells (indicated as blue cells with black melanin granules). At the left side, the retinal blood vessels are separated from sterile vitreous fluid by the internal limiting membrane (continuous black line).