Bioactive Materials · 5 authors, 4 centres
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This narrative review surveys the evolution of in vitro and in vivo models of the outer blood-retina barrier (oBRB), covering cell sources, biomaterial membranes, co-culture systems, and preclinical/clinical trials for RPE cellular therapy. It concludes that increasing model complexity through iPSC-derived cells, microfluidic chips, and multi-cell-type co-cultures is advancing the field toward more physiologically relevant retinal disease modelling and transplantation.
This narrative review provides a comprehensive overview of outer blood-retina barrier (oBRB) engineering, spanning in vitro models and in vivo implantation strategies. The authors describe how model complexity has increased over three decades, progressing from simple Transwell inserts to microfluidic chips enabling 3D tissue structuring and fluid flow. Key cell sources are compared, including ARPE-19 cell lines, primary RPE cells, human embryonic stem cell-derived RPE, and human induced pluripotent stem cell-derived RPE, with hiPSC-RPE identified as the most promising for both modelling and cellular therapy due to reduced immunological rejection risk. Co-culture models incorporating retinal pigment epithelium with choroidal endothelial cells, pericytes, and fibroblasts are highlighted for improved recapitulation of native tissue behaviour and pathological conditions. Five implants have reached clinical trials with promising early results. Limitations include the predominant focus on the RPE layer alone and ethical concerns with embryonic cell sources.
