Retinal Microvasculature-on-a-Chip for Modeling VEGF-Induced Permeability.

Relevant human in vitro models of the retinal microvasculature can be used to study the role of disease mediators on retinal barrier dysfunction and assess the efficacy of early drug candidates. This chapter describes an organ-on-a-chip model of the retinal microvasculature that allows for facile quantification of barrier permeability in response to leakage mediators, such as Vascular Endothelial Growth Factor (VEGF), and enables screening of VEGF-induced permeability inhibitors. This chapter also presents an automated confocal imaging method for the visualization of endothelial tube morphology as an additional measure of barrier integrity.

Human Retinal Microvasculature-on-a-Chip for Drug Discovery.

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.