3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration.

Autor:	Manian KV; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA., Galloway CA; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA; Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14620, USA., Dalvi S; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA., Emanuel AA; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA., Mereness JA; Department of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA; Department of Orthopedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA; Center for Oral Biology, University of Rochester, Rochester, NY 14642, USA; Department of Environmental Medicine, University of Rochester, Rochester, NY 14642 USA., Black W; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA., Winschel L; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA., Soto C; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA., Li Y; Department of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA., Song Y; Department of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA., DeMaria W; Department of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA., Kumar A; Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA., Slukvin I; Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA; Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53715, USA., Schwartz MP; NSF Center for Sustainable Nanotechnology, Department of Chemistry, University of Wisconsin, Madison, WI 53706, USA; Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53715, USA., Murphy WL; Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53715, USA; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53715, USA., Anand-Apte B; Department of Ophthalmic Research, Cole Eye Institute and Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA., Chung M; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Center for Visual Science, University of Rochester, Rochester, NY 14620, USA., Benoit DSW; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA; Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA; Department of Orthopedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA; Center for Oral Biology, University of Rochester, Rochester, NY 14642, USA; Department of Environmental Medicine, University of Rochester, Rochester, NY 14642 USA; UR Stem Cell and Regenerative Medicine Center, Rochester, NY 14620, USA; Materials Science Program, University of Rochester, Rochester, NY 14620, USA; Department of Chemical Engineering, University of Rochester, NY 14620, USA., Singh R; Department of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA; Department of Orthopedics and Center for Musculoskeletal Research, University of Rochester, Rochester, NY 14642, USA; Center for Visual Science, University of Rochester, Rochester, NY 14620, USA; UR Stem Cell and Regenerative Medicine Center, Rochester, NY 14620, USA. Electronic address: ruchira_singh@urmc.rochester.edu.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2021 May 06; Vol. 28 (5), pp. 846-862.e8. Date of Electronic Publication: 2021 Mar 29.
DOI:	10.1016/j.stem.2021.02.006
Abstrakt:	The retinal pigment epithelium (RPE)-choriocapillaris (CC) complex in the eye is compromised in age-related macular degeneration (AMD) and related macular dystrophies (MDs), yet in vitro models of RPE-CC complex that enable investigation of AMD/MD pathophysiology are lacking. By incorporating iPSC-derived cells into a hydrogel-based extracellular matrix, we developed a 3D RPE-CC model that recapitulates key features of both healthy and AMD/MD eyes and provides modular control over RPE and CC layers. Using this 3D RPE-CC model, we demonstrated that both RPE- and mesenchyme-secreted factors are necessary for the formation of fenestrated CC-like vasculature. Our data show that choroidal neovascularization (CNV) and CC atrophy occur in the absence of endothelial cell dysfunction and are not necessarily secondary to drusen deposits underneath RPE cells, and CC atrophy and/or CNV can be initiated systemically by patient serum or locally by mutant RPE-secreted factors. Finally, we identify FGF2 and matrix metalloproteinases as potential therapeutic targets for AMD/MDs. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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