Title: Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration
Author: Song, Min Jae, Quinn, Russ, Nguyen, Eric, Hampton, Christopher, Sharma, Ruchi, Park, Tea Soon, Koster, Cline, Voss, Ty, Tristan, Carlos, Weber, Claire, Singh, Anju, Dejene, Roba, Bose, Devika, Chen, Yu-Chi, Derr, Paige, Derr, Kristy, Michael, Sam, Barone, Francesca, Chen, Guibin, Boehm, Manfred, Maminishkis, Arvydas, Singec, Ilyas, Ferrer, Marc, Bharti, Kapil
Issue&Volume: 2022-12-22
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.
DOI: 10.1038/s41592-022-01701-1
Source: https://www.nature.com/articles/s41592-022-01701-1
Nature Methods：《自然—方法学》，创刊于2004年。隶属于施普林格·自然出版集团，最新IF：47.99
官方网址：https://www.nature.com/nmeth/
投稿链接：https://mts-nmeth.nature.com/cgi-bin/main.plex
本期文章：《自然—方法学》：Online/在线发表
