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Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.
Song, Min Jae; Quinn, Russ; Nguyen, Eric; Hampton, Christopher; Sharma, Ruchi; Park, Tea Soon; Koster, Céline; 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.
Afiliación
  • Song MJ; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Quinn R; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Nguyen E; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Hampton C; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Sharma R; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Park TS; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Koster C; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Voss T; Department of Human Genetics Amsterdam, Section of Ophthalmogenetics, Amsterdam University Medical Centers (AUMC), University of Amsterdam, Amsterdam, The Netherlands.
  • Tristan C; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Weber C; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Singh A; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Dejene R; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Bose D; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Chen YC; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Derr P; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Derr K; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Michael S; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Barone F; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Chen G; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Boehm M; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Maminishkis A; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
  • Singec I; National Eye Institute, National Institutes of Health, Bethesda, USA.
  • Ferrer M; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
  • Bharti K; National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, USA.
Nat Methods ; 20(1): 149-161, 2023 01.
Article en En | MEDLINE | ID: mdl-36550275
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Epitelio Pigmentado de la Retina / Degeneración Macular Límite: Humans Idioma: En Revista: Nat Methods Asunto de la revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Epitelio Pigmentado de la Retina / Degeneración Macular Límite: Humans Idioma: En Revista: Nat Methods Asunto de la revista: TECNICAS E PROCEDIMENTOS DE LABORATORIO Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos