TY - JOUR
KW - Biological models
KW - biomaterials
KW - Experimental models of disease
KW - Stem-cell research
KW - translational research
AU - Min Jae Song
AU - Russ Quinn
AU - Eric Nguyen
AU - Christopher Hampton
AU - Ruchi Sharma
AU - Tea Soon Park
AU - Céline Koster
AU - Ty Voss
AU - Carlos Tristan
AU - Claire Weber
AU - Anju Singh
AU - Roba Dejene
AU - Devika Bose
AU - Yu-Chi Chen
AU - Paige Derr
AU - Kristy Derr
AU - Sam Michael
AU - Francesca Barone
AU - Guibin Chen
AU - Manfred Boehm
AU - Arvydas Maminishkis
AU - Ilyas Singec
AU - Marc Ferrer
AU - Kapil Bharti
AB - 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.
BT - Nature Methods
DA - 2023-01
DO - 10.1038/s41592-022-01701-1
IS - 1
LA - en
N2 - 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.
PY - 2023
SP - 149
EP - 161
T2 - Nature Methods
TI - Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration
UR - https://www.nature.com/articles/s41592-022-01701-1
VL - 20
Y2 - 2023-02-02
SN - 1548-7105
ER -