Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability

Journal of Biochemical and Molecular Toxicology
Nicoline M KorthagenWillem A Dik

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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Citations

Jan 11, 2016·Annals of the New York Academy of Sciences·Madhu M OusephQing Jun Wang
Mar 11, 2017·Eye·I H YusufS M Downes
Nov 9, 2019·Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft·A RickmannG Szurman
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Jul 3, 2021·Journal of Biomaterials Applications·Baltej DhillonSudipta Seal

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