Human Retinal Microvasculature-on-a-Chip for Drug Discovery.
Héloïse RagelleKaren DernickSonia KhemaisCordula KepplerLucien CousinYohan FarouzChris LoucheSascha FauserStefan KustermannMark W TibbittPeter D WestenskowPublished in: Advanced healthcare materials (2020)
Retinal cells within neurovascular units generate the blood-retinal barrier (BRB) to regulate the local retinal microenvironment and to limit access to inflammatory cells. Breakdown of the endothelial junctional complexes in the BRB negatively affects neuronal signaling and ultimately causes vision loss. As new therapeutics are being developed either to prevent barrier disruption or to restore barrier function, access to physiologically relevant human in vitro tissue models that recapitulate important features of barrier biology is essential for disease modeling, target validation, and toxicity assessment. Here, a tunable organ-on-a-chip model of the retinal microvasculature using human retinal microvascular endothelial cells with integrated flow is described. Automated imaging and image analysis methods are employed for facile screening of leakage mediators and cytokine inhibitors on barrier properties. The developed retinal microvasculature-on-a-chip will enable improved understanding of BRB biology and provide an additional tool for drug discovery.
Keyphrases
- endothelial cells
- optical coherence tomography
- diabetic retinopathy
- drug discovery
- optic nerve
- induced apoptosis
- high throughput
- oxidative stress
- stem cells
- high glucose
- circulating tumor cells
- cell cycle arrest
- pluripotent stem cells
- deep learning
- small molecule
- high resolution
- mass spectrometry
- signaling pathway
- blood brain barrier
- brain injury
- vascular endothelial growth factor
- photodynamic therapy
- endoplasmic reticulum stress
- cell proliferation
- single cell
- fluorescence imaging
- energy transfer