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Modelling Macular Edema: The Effect of IL-6 and IL-6R Blockade on Human Blood-Retinal Barrier Integrity In Vitro

Mesquida, M; Drawnel, F; Lait, PJ; Copland, DA; Stimpson, ML; Llorenc, V; Sainz de la Maza, M; ... Molins, B; + view all (2019) Modelling Macular Edema: The Effect of IL-6 and IL-6R Blockade on Human Blood-Retinal Barrier Integrity In Vitro. Translational Vision Science & Technology , 8 (5) , Article 32. 10.1167/tvst.8.5.32. Green open access

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Abstract

Purpose: Macular edema (ME) is a leading cause of visual loss in a range of retinal diseases and despite the use of antivascular endothelial growth factor (anti-VEGF) agents, its successful treatment remains a major clinical challenge. Based on the indirect clinical evidence that interleukin-6 (IL-6) is a key additional candidate mediator of ME, we interrogated the effect of IL-6 on blood–retinal barrier (BRB) integrity in vitro. Methods: Human retinal pigment epithelial cell (ARPE-19) and human retinal microvascular endothelial cell (HRMEC) monolayers were used to mimic the outer and inner BRB, respectively. Their paracellular permeability was assessed by measuring the passive permeation of 40 kDa fluorescein isothiocyanate (FITC)-dextran across confluent cells in the presence of IL-6. Transendothelial/epithelial electrical resistance (TEER) then was measured and the distribution of the tight junction protein ZO-1 was assessed by immunofluorescence using confocal microscopy. Results: Treatment with IL-6 for 48 hours significantly increased the diffusion rate of FITC-dextran, decreased TEER, and disrupted the distribution of ZO-1 in ARPE-19 cells, which constitutively express the IL-6 transmembrane receptor, and this was reversed with IL-6R blockade. In contrast, IL-6 did not affect the paracellular permeability, TEER, or ZO-1 distribution in HRMECs. Conclusions: These in vitro data support the hypothesis that IL-6 reversibly disrupts the integrity of ARPE-19 cells, but it does not affect HRMECs. Translational Relevance: IL-6 is a candidate therapeutic target in the treatment of outer BRB driven ME.

Type: Article
Title: Modelling Macular Edema: The Effect of IL-6 and IL-6R Blockade on Human Blood-Retinal Barrier Integrity In Vitro
Open access status: An open access version is available from UCL Discovery
DOI: 10.1167/tvst.8.5.32
Publisher version: https://doi.org/10.1167/tvst.8.5.32
Language: English
Additional information: © 2019 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10086043
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