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Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability
Nicoline M Korthagen1, Jeroen Bastiaans1, Jan C van Meurs2,3
1Department of Immunology, Erasmus MC, University Medical Center, P.O. Box 2060, 3000, CB, Rotterdam, The Netherlands.
Journal of Biochemical and Molecular Toxicology
|March 11, 2015
Summary
Chloroquine (CQ) and hydroxychloroquine (HCQ) rapidly increase retinal pigment epithelial (RPE) cell layer permeability. This effect occurs before significant cell death, suggesting a mechanism for drug-induced retinopathy.
Area of Science:
- Ophthalmology
- Pharmacology
- Cell Biology
Background:
- Antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) are prescribed for inflammatory conditions.
- CQ and HCQ can cause retinopathy and vision loss as adverse effects.
- The precise mechanism of CQ/HCQ-induced retinopathy remains under investigation.
Purpose of the Study:
- To investigate the impact of CQ and HCQ on the barrier integrity of retinal pigment epithelial (RPE) cell monolayers in vitro.
- To determine if CQ and HCQ affect RPE cell viability and tight junction molecule expression.
- To elucidate the early effects of CQ and HCQ on the blood-retinal barrier.
Main Methods:
- ARPE-19 cell monolayers were utilized to model the RPE layer.
- Permeability was assessed using Fluorescein isothiocyanate (FITC)-labeled dextran.
- Cell death and mRNA expression of tight junction proteins (claudin-1, occludin, zonula occludens-1) were analyzed.
Main Results:
- CQ and HCQ significantly elevated ARPE-19 monolayer permeability at 3 and 18 hours, respectively.
- Increased mRNA levels for claudin-1 and occludin were observed.
- Cytotoxicity was evident only after 18 hours of exposure.
- The enhanced permeability occurred independently of significant cell death or altered expression of zonula occludens-1, claudin-1, and occludin.
Conclusions:
- CQ and HCQ rapidly disrupt RPE barrier function in vitro.
- This disruption of RPE permeability precedes significant cytotoxicity.
- These findings suggest that increased RPE permeability may be an early event contributing to blood-retinal barrier breakdown in CQ/HCQ-induced retinopathy.
