The outer blood-retinal barrier is a key component in the transport between neural retinal tissue and the vascular network and it is formed by the retinal pigment epithelium, the basal membrane and the choroidal bed. Due to its critical role, there is an urgent need to develop translational in vitro models that faithfully replicate in vivo physiology to investigate pathological mechanisms involving barrier dysfunction and potential therapeutic strategies. Here, human immortalised retinal pigment epithelial cells and human umbilical vein endothelial cells were used to develop a microfluidic 3D organ-on-a-chip system of the outer blood-retinal barrier. The results showed that it was possible to successfully culture monolayers of both cells types and the presence of 3D vascular structures. Moreover, there were heterogeneous vessel densities and diameters. Furthermore, it was possible to detect barrier permeability upon oxidative challenge with techniques used in clinical tests. Overall, the researchers propose a 3D microfluidic organ-on-a-chip model that can replicate in vitro several physiological features of the outer blood-retinal barrier and which can potentially be used to investigate pathological mechanisms using clinically relevant readouts.
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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