Modeling early pathophysiological phenotypes of diabetic retinopathy in a human inner blood-retinal barrier-on-a-chip.

Diabetic retinopathy (DR) is a microvascular disorder characterized by inner blood-retinal barrier (iBRB) breakdown and irreversible vision loss. While the symptoms of DR are known, disease mechanisms including basement membrane thickening, pericyte dropout and capillary damage remain poorly understood and interventions to repair diseased iBRB microvascular networks have not been developed. In addition, current approaches using animal models and in vitro systems lack translatability and predictivity to finding new target pathways.

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.

Microphysiological Neurovascular Barriers to Model the Inner Retinal Microvasculature.

Blood-neural barriers regulate nutrient supply to neuronal tissues and prevent neurotoxicity. In particular, the inner blood-retinal barrier (iBRB) and blood-brain barrier (BBB) share common origins in development, and similar morphology and function in adult tissue, while barrier breakdown and leakage of neurotoxic molecules can be accompanied by neurodegeneration. Therefore, pre-clinical research requires human in vitro models that elucidate pathophysiological mechanisms and support drug discovery, to add to animal in vivo modeling that poorly predict patient responses.

Additive manufacturing in drug delivery: Innovative drug product design and opportunities for industrial application.

Additive manufacturing (AM) or 3D printing is enabling new directions in product design. The adoption of AM in various industrial sectors has led to major transformations. Similarly, AM presents new opportunities in the field of drug delivery, opening new avenues for improved patient care.

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.