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

Research output: Contribution to journalArticleResearchpeer-review


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 languageEnglish
Pages (from-to)299-304
Number of pages6
JournalJournal of Biochemical and Molecular Toxicology
Issue number7
Publication statusPublished - Jul 2015


  • Antimalarials/pharmacology
  • Blood-Retinal Barrier/drug effects
  • Chloroquine/pharmacology
  • Claudin-1/drug effects
  • Gene Expression Regulation
  • Humans
  • Hydroxychloroquine/pharmacology
  • Occludin/drug effects
  • Permeability/drug effects
  • RNA, Messenger
  • Retinal Pigment Epithelium/drug effects
  • Tight Junctions/drug effects


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