Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability |
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| Authors: | Nicoline M Korthagen Jeroen Bastiaans Jan C van Meurs Kiki van Bilsen P Martin van Hagen Willem A Dik |
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| Institution: | 1. Department of Immunology, Erasmus MC, University Medical Center, CB, Rotterdam, The Netherlands;2. The Rotterdam Eye Hospital, LM, Rotterdam, The Netherlands;3. Department of Ophthalmology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands;4. Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands |
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| Abstract: | Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are widely used as antiinflammatory drugs, but side effects include retinopathy and vision loss. The objective of this study was to examine the effect of CQ and HCQ on the barrier integrity of retinal pigment epithelial (RPE) cell monolayers in vitro. Permeability of ARPE‐19 cell monolayers was determined using Fluorescein isothiocyanate (FITC)‐labeled dextran. The influence of CQ and HCQ on cell death and the expression tight junction molecules was examined. CQ and HCQ significantly increased ARPE‐19 monolayer permeability after 3 and 18 h, respectively, and enhanced mRNA levels for claudin‐1 and occludin. Cytotoxicity was only observed after 18 h exposure. Thus, CQ and HCQ rapidly enhance RPE barrier permeability in vitro, independent of cytotoxicity or loss of zonula occludens‐1, claudin‐1, and occludin expression. Our findings suggest that CQ/HCQ‐induced permeability of the RPE layer may contribute to blood–retinal barrier breakdown in case of CQ/HCQ‐induced retinopathy. |
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| Keywords: | retinal pigment epithelial cell barrier function chloroquine hydroxychloroquine Transwell tight‐junctions |
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