Inflammatory cytokines as mediators of retinal endothelial barrier dysfunction in non‐infectious uveitis

Abstract

Characterised by intraocular inflammation, non‐infectious uveitis includes a large group of autoimmune and autoinflammatory diseases that either involve the eye alone or have both ocular and systemic manifestations. When non‐infectious uveitis involves the posterior segment of the eye, specifically the retina, there is substantial risk of vision loss, often linked to breakdown of the inner blood‐retinal barrier. This barrier is formed by non‐fenestrated retinal vascular endothelial cells, reinforced by supporting cells that include pericytes, Müller cells and astrocytes. Across the published literature, a group of inflammatory cytokines stand out as prominent mediators of intraocular inflammation, with effects on the retinal endothelium that may contribute to breakdown of the inner blood‐retinal barrier, namely tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17 and chemokine C‐C motif ligand (CCL)2. This article reviews the function of each cytokine and discusses the evidence for their involvement in retinal endothelial barrier dysfunction in non‐infectious uveitis, including basic laboratory investigations, studies of ocular fluids collected from patients with non‐infectious uveitis, and results of clinical treatment trials. The review also outlines gaps in knowledge in this area. Understanding the disease processes at a molecular level can suggest treatment alternatives that are directed against appropriate biological targets to protect the posterior segment of eye and preserve vision in non‐infectious uveitis.

Case Report: Longitudinal Evaluation and Treatment of a Melanoma-Associated Retinopathy Patient

“…As in ammation is a known modulator of BRB integrity (Byrne et al, 2021;Capaldo et al, 2014;Ferreira et al, 2023;Frank and Lisanti, 2008;Ogura et al, 2017), we sought to examine the in ammatory state of the eye to assess the potential for BRB damage in this MAR patient. Our cytokine array detected a heightened in ammatory state in the patient's aqueous humor on all three collection dates when compared to a non-MAR control cohort (Figure 1B).…”

“…Fifteen cytokines, which were undetectable in a non-MAR control cohort, appear elevated in the MAR patient, several of which have been implicated in regulating BRB integrity, including IL-1β, IL-17A, TNFα , and VEGF-A (Figure1B)(Byrne et al, 2021;Capaldo et al, 2014;Capaldo and Nusrat, 2009;Ferreira et al, 2023;Frank and Lisanti, 2008). In accordance with the heightened in ammatory state, evidence of vascular leakage indicative of a compromised BRB was visible in the patient's uorescein angiograms on September 1, 2021 (Figure1A).…”

Circulating miRNAs and Preeclampsia: From Implantation to Epigenetics

“…Probably, the initial defect in placentation and vascularization in the placenta bed due to poor trophoblast invasion of the spiral arteries [17][18][19] leads to an inappropriate activation of the immune system [20], as it occurs in recurrent miscarriage [21]. It is known that oxidative stress and inflammation are involved in endothelial dysfunction [22][23][24][25][26][27], a key process underlying several diseases including preeclampsia [28][29][30][31][32]. Hypoxia due to inadequate spiral artery remodeling compromises the placental endothelial 2 of 24 function [33], which results in an oxidative stress condition [34,35], made worse by an increased production of nitric oxide [36,37].…”

Immune Factors, Immune Cells and Inflammatory Diseases

“…The development and function of immune cells, extending to the regulation of inflammation, is moderated by a rich network of immune factors, notably including cytokines, chemokines, growth factors and other signaling proteins [8][9][10], as well as the numerous molecules that serve to regulate their action [11][12][13]. These proteins are required for normal immune cell development and function, but many are also perturbed in a variety of inflammatory disease states [14][15][16].…”