3D Bioprinted retina models for drug screening

National Center For Advancing Translational Sciences

Investigators

Linked publications, trials & patents

Abstract

An engineered ocular tissue of outer blood retina barrier containing RPE and three dimensional (3D) vascularized tissue has been produced using bioprinting techniques with human induced pluripotent stem cells. It successfully recapitulates features of choriocapillaris and components of Bruchs membranes including RPE induced vascular endothelial fenestration and extracellular matrix formation. We have further demonstrated that HIF-1 induced angiogenesis towards RPE in the tissue and the reduction of the induced angiogenesis with improved barrier functions by bevacizumab treatment. We have also explored the usefulness of this 3D retina tissue model to investigate Zika virus infection and demonstrated viral infection in the tissue and disruption of barrier function. More recently, we have incorporated macrophages in the outer blood retina barrier model and have shown that macrophages induce choroidal senescence and cause neovascular AMD-like phenotypes. This 3D vascularized ocular tissue model therefore provides extensive opportunities to study underlying mechanisms of relevant diseases and the development of therapeutics. This year we have worked on automating with process of assembling this bioprinted tissue models. So far, we have been successful in assembling the RPE layer in a fully automate manner for ~ 5 weeks. As an initial proof-of-concept, we will test a library of compounds for toxic effects on the retina structure.