Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability

Nicoline M Korthagen; Jeroen Bastiaans; Jan C van Meurs; Kiki van Bilsen; P Martin van Hagen; Willem A Dik

doi:10.1002/jbt.21696

Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability

Nicoline M Korthagen, Jeroen Bastiaans, Jan C van Meurs, Kiki van Bilsen, P Martin van Hagen, Willem A Dik

Erasmus University Medical Center Rotterdam

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	299-304
Journal	Journal of Biochemical and Molecular Toxicology
Volume	29
Issue number	7
DOIs	https://doi.org/10.1002/jbt.21696
Publication status	Published - Jul 2015

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10.1002/jbt.21696

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@article{e72cf83224d34d15b7b5acd60a863d66,

title = "Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability",

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.",

author = "Korthagen, \{Nicoline M\} and Jeroen Bastiaans and \{van Meurs\}, \{Jan C\} and \{van Bilsen\}, Kiki and \{van Hagen\}, \{P Martin\} and Dik, \{Willem A\}",

year = "2015",

month = jul,

doi = "10.1002/jbt.21696",

language = "English",

volume = "29",

pages = "299--304",

journal = "Journal of Biochemical and Molecular Toxicology",

issn = "1095-6670",

publisher = "Wiley",

number = "7",

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T1 - Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability

AU - Korthagen, Nicoline M

AU - Bastiaans, Jeroen

AU - van Meurs, Jan C

AU - van Bilsen, Kiki

AU - van Hagen, P Martin

AU - Dik, Willem A

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

U2 - 10.1002/jbt.21696

DO - 10.1002/jbt.21696

M3 - Article

C2 - 25752684

SN - 1095-6670

VL - 29

SP - 299

EP - 304

JO - Journal of Biochemical and Molecular Toxicology

JF - Journal of Biochemical and Molecular Toxicology

IS - 7

ER -

Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability

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