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Issue 2, 2021
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Microfluidic organ-on-a-chip model of the outer blood–retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure

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Abstract

The outer blood–retinal barrier (oBRB) tightly controls the transport processes between the neural tissue of the retina and the underlying blood vessel network. The barrier is formed by the retinal pigment epithelium (RPE), its basal membrane and the underlying choroidal capillary bed. Realistic three-dimensional cell culture based models of the oBRB are needed to study mechanisms and potential treatments of visual disorders such as age-related macular degeneration that result from dysfunction of the barrier tissue. Ideally, such models should also include clinically relevant read-outs to enable translation of experimental findings in the context of pathophysiology. Here, we report a microfluidic organ-on-a-chip model of the oBRB that contains a monolayer of human immortalized RPE and a microvessel of human endothelial cells, separated by a semi-permeable membrane. Confluent monolayers of both cell types were confirmed by fluorescence microscopy. The three-dimensional vascular structures within the chip were imaged by optical coherence tomography: a medical imaging technique, which is routinely applied in ophthalmology. Differences in diameters and vessel density could be readily detected. Upon inducing oxidative stress by treating with hydrogen peroxide (H2O2), a dose dependent increase in barrier permeability was observed by using a dynamic assay for fluorescence tracing, analogous to the clinically used fluorescence angiography. This organ-on-a-chip of the oBRB will allow future studies of complex disease mechanisms and treatments for visual disorders using clinically relevant endpoints in vitro.

Graphical abstract: Microfluidic organ-on-a-chip model of the outer blood–retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure

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Supplementary files

Article information


Submitted
19 Jun 2020
Accepted
02 Dec 2020
First published
15 Dec 2020

This article is Open Access

Lab Chip, 2021,21, 272-283
Article type
Paper

Microfluidic organ-on-a-chip model of the outer blood–retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure

Y. B. Arık, W. Buijsman, J. Loessberg-Zahl, C. Cuartas-Vélez, C. Veenstra, S. Logtenberg, A. M. Grobbink, P. Bergveld, G. Gagliardi, A. I. den Hollander, N. Bosschaart, A. van den Berg, R. Passier and A. D. van der Meer, Lab Chip, 2021, 21, 272
DOI: 10.1039/D0LC00639D

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    [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
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    [Original citation] - Published by The Royal Society of Chemistry.

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