Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability.
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.
Department of Immunology, Erasmus MC, University Medical Center, P.O. Box 2060, 3000, CB, Rotterdam, The Netherlands.
Nicoline M
NM
Korthagen
Department of Immunology, Erasmus MC, University Medical Center, P.O. Box 2060, 3000, CB, Rotterdam, The Netherlands.
Jeroen
J
Bastiaans
The Rotterdam Eye Hospital, P.O. Box 70030, 3000, LM, Rotterdam, The Netherlands.|Department of Ophthalmology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Jan C
JC
van Meurs
Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Kiki
K
van Bilsen
Department of Immunology, Erasmus MC, University Medical Center, P.O. Box 2060, 3000, CB, Rotterdam, The Netherlands.|The Rotterdam Eye Hospital, P.O. Box 70030, 3000, LM, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
P Martin
PM
van Hagen
Department of Immunology, Erasmus MC, University Medical Center, P.O. Box 2060, 3000, CB, Rotterdam, The Netherlands.
Willem A
WA
Dik
D000962:Antimalarials / Q000494:pharmacology*; D001813:Blood-Retinal Barrier / Q000187:drug effects* / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology*; D062445:Claudin-1 / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D062793:Occludin / Q000187:drug effects / Q000235:genetics; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism
D000962:Antimalarials; C568108:CLDN1 protein, human; D062445:Claudin-1; C568985:OCLN protein, human; D062793:Occludin; D012333:RNA, Messenger; D006886:Hydroxychloroquine; D002738:Chloroquine
Transwell; barrier function; chloroquine; hydroxychloroquine; retinal pigment epithelial cell; tight-junctions