Abstract
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. Advanced cellular models such as microphysiological systems (MPS) recapitulate tissue organization and function in many organ-specific contexts, providing physiological relevance, potential for customization to different population groups, and scalability for drug screening purposes. While human-based MPS have been developed for tissues such as lung, gut, brain and tumors, few comprehensive models exist for ocular tissues and iBRB modeling. Recent BBB in vitro models using human cells of the neurovascular unit (NVU) showed physiological morphology and permeability values, and reproduced brain neurological disorder phenotypes that could be applicable to modeling the iBRB. Here, we describe similarities between iBRB and BBB properties, compare existing neurovascular barrier models, propose leverage of MPS-based strategies to develop new iBRB models, and explore potentials to personalize cellular inputs and improve pre-clinical testing.
Highlights
The blood–brain barrier (BBB) controls molecular transport to brain neural tissue. These blood–neural barriers are composed of perivascular mural and glial cells that share a common origin in the central nervous system (CNS) vascular development [2,3], form the retinal and brain neurovascular units (NVUs) and play multiple roles in barrier stabilization and maintenance to protect against neurotoxicity [4,5,6]
Microvascular diseases linked to chronic or genetic conditions often lead to barrier breakdown and neurodegeneration in the retina or brain. inner blood-retinal barrier (iBRB) dysfunction and vascular leakage are associated with some of the most predominant ocular diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) [10,11]
While bioengineering approaches to model BBB features have already been extensively reviewed [22,25,33,34,35,36,37,38], we propose to harness the strengths of existing MPSbased strategies to generate better iBRB models
Summary
The blood–brain barrier (BBB) controls molecular transport to brain neural tissue These blood–neural barriers are composed of perivascular mural and glial cells that share a common origin in the central nervous system (CNS) vascular development [2,3], form the retinal and brain neurovascular units (NVUs) and play multiple roles in barrier stabilization and maintenance to protect against neurotoxicity [4,5,6]. Human-based advanced cellular models have the potential to be customized to specific patient groups/populations and to be scalable for drug discovery purposes Taken together, these BBB in vitro models showed physiologically relevant morphology and permeability values, and reproduced pathophysiological phenotypes such as vascular leakage and neurodegeneration [30,31,32]. We explore potentials to further personalize cellular inputs and improve pre-clinical testing using MPS
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