@article{991,
  keywords = {Biological models, biomaterials, Experimental models of disease, Stem-cell research, translational research},
  author = {Min Jae Song and Russ Quinn and Eric Nguyen and Christopher Hampton and Ruchi Sharma and Tea Soon Park and Céline Koster and Ty Voss and Carlos Tristan and Claire Weber and Anju Singh and Roba Dejene and Devika Bose and Yu-Chi Chen and Paige Derr and Kristy Derr and Sam Michael and Francesca Barone and Guibin Chen and Manfred Boehm and Arvydas Maminishkis and Ilyas Singec and Marc Ferrer and Kapil Bharti},
  title = {Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration},
  abstract = {Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top. In this 3D-oBRB model, a fully-polarized RPE monolayer provides barrier resistance, induces choriocapillaris fenestration, and supports the formation of Bruch’s-membrane-like structure by inducing changes in gene expression in cells of the choroid. Complement activation in the 3D-oBRB triggers dry AMD phenotypes (including subRPE lipid-rich deposits called drusen and choriocapillaris degeneration), and HIF-α stabilization or STAT3 overactivation induce choriocapillaris neovascularization and type-I wet AMD phenotype. The 3D-oBRB provides a physiologically relevant model to studying RPE–choriocapillaris interactions under healthy and diseased conditions.},
  year = {2023},
  journal = {Nature Methods},
  volume = {20},
  pages = {149-161},
  month = {2023-01},
  issn = {1548-7105},
  url = {https://www.nature.com/articles/s41592-022-01701-1},
  doi = {10.1038/s41592-022-01701-1},
  language = {en},
}