| Autor: |
Christopher Hampton, Ty C. Voss, Anju Singh, Kapil Bharti, Arvydas Maminishkis, Eric Nguyen, Roba Dejene, Claire Malley, Paige Derr, Ilyas Singeç, Céline Koster, Kristy Derr, Russell Quinn, Francesca Barone, Marc Ferrer, Carlos A. Tristan, Tea Soon Park, Ruchi Sharma, Sam Michael, Min Jae Song, Devika Bose |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-135775/v1 |
| Popis: |
Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by Retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris. The mechanism of AMD initiation and progression remain poorly understood due to the lack of physiologically relevant oBRB models. We engineered a native-like 3D-oBRB tissue 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, a fully-polarized RPE monolayer with apical processes and basal infoldings provides barrier resistance, induces fenestration and choroid-specific gene expression in the choriocapillaris, and supports the formation of a Bruch’s-like membrane that allows tissue integration in rat eyes. Complement activation in the 3D-oBRB triggers dry-AMD phenotypes (including subRPE drusen and choriocapillaris degeneration), and hypoxia activated HIF-α induces wet-AMD phenotypes (choriocapillaris neovascularization). Anti-VEGF drug treatment suppresses neovascularization - validating this model for clinical translation and drug discovery. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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