葡萄膜炎或眼内炎症是一种潜在的致盲性疾病，主要影响劳动年龄人口。细胞因子肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-1β 在非感染性葡萄膜炎的发病机制中发挥作用，并与主要由视网膜内皮细胞组成的内部血-视网膜屏障的破坏有关。细胞，导致黄斑水肿和血管渗漏。然而，TNF-α和IL-1β对人视网膜内皮功能的影响尚不完全清楚。在这项工作中，我们研究了 TNF-α 和 IL-1β 对人视网膜内皮细胞生物学多个方面的影响。通过实时生物传感器，分析了TNF-α和IL-1β对视网膜内皮细胞屏障形成的影响。通过 RT-qPCR 和免疫标记评估连接成分的变化。通过细胞增殖和流式细胞术研究评估细胞存活、坏死和凋亡。肿瘤坏死因子-α和IL-1β损害了视网膜内皮细胞屏障的电阻，而添加潜在的屏障损害细胞因子IL-6并没有增强TNF-α和IL-1β的作用。编码闭合小带 (ZO)-1 的基因转录水平降低，而 TNF-α 和 IL-1β 改变了 ZO-1 蛋白结构。两种细胞因子都会影响人视网膜内皮细胞的增殖和活力，而只有 TNF-α 会增加坏死率。这些结果表明 TNF-α 和 IL-1β 是非感染性葡萄膜炎视网膜内皮功能障碍的重要驱动因素，这表明在治疗黄斑水肿和血管渗漏等葡萄膜炎并发症时，靶向这些细胞因子至关重要。版权所有 © 2023 作者（s）。由爱思唯尔有限公司出版。保留所有权利。

Uveitis, or intraocular inflammation, is a potentially blinding condition that mostly affects the working-age population. The cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play a role in the pathogenesis of non-infectious uveitis and have been linked to the breakdown of the inner blood-retinal barrier, composed mainly of retinal endothelial cells, leading to macular oedema and vascular leakage. However, the effects of TNF-α and IL-1β on human retinal endothelial function are not fully understood. In this work, we investigated the impact of TNF-α and IL-1β on several aspects of human retinal endothelial cell biology. Through a real-time biosensor, the impact of TNF-α and IL-1β on formation of a retinal endothelial cell barrier was analyzed. Changes in junctional components were assessed via RT-qPCR and immunolabelling. Cell survival, necrosis and apoptosis were appraised via cell proliferation and flow cytometric studies. Tumor necrosis factor-α and IL-1β impaired the electrical resistance of the retinal endothelial cell barrier, while the addition of a potentially barrier-impairing cytokine, IL-6, did not enhance the effect of TNF-α and IL-1β. Level of the gene transcript encoding zonula occludens (ZO)-1 was diminished, while ZO-1 protein configuration was changed by TNF-α and IL-1β. Both cytokines affected human retinal endothelial cell proliferation and viability, while only TNF-α increased rates of necrosis. These results indicate that TNF-α and IL-1β are important drivers of retinal endothelial dysfunction in non-infectious uveitis, suggesting that targeting these cytokines is critical when treating complications of uveitis, such as macular oedema and vascular leakage.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.