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

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, Muller 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)-alpha, interleukin (IL)-1 beta, 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. Non-infectious uveitis has a range of ocular and systemic autoimmune and autoinflammatory causes. When the retina is involved, blood-retinal barrier breakdown can lead to vision loss. Specific cytokines stand out as promoting intraocular inflammation. This article reviews the involvement of inflammatory cytokines - including tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, IL-8, IL-17 and chemokine C-C motif ligand (CCL)2 - in non-infectious uveitis. Their levels in ocular fluids, their effects on the endothelial barrier, and the results of clinical treatment trials are discussed.image