ArticleCell stem cell2021
3D iPSC modeling of the retinal pigment epithelium-choriocapillaris complex identifies factors involved in the pathology of macular degeneration.
Erratum issuedOpen access · bronzeAbstract read
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Article in Cell stem cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers.
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26citing papers in PubMed
9.0field-weighted citation impact, top 1% of its field
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Who cites it
26 citing papers in PubMed, 63 citations in OpenAlex.
- Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.Journal of extracellular biology · 2026Article
- 3D epigenomic landscape of the human retinal pigment epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration.Genome medicine · 2026Article
- Bemarituzumab Suppresses Choroidal Neovascularization in Mice by Downregulating Melanoma Cell Adhesion Molecule and Yes-Associated Protein 1.ACS pharmacology & translational science · 2026Article
- Personalized Models of Biological Barriers and Their Diseases: Recent Progress with Organs-On-Chips.Advanced biology · 2026Review
- The influence of femtosecond laser intrastromal lenticules on the characteristics and maturity in tissue-engineered stem cell-derived retinal pigment epithelium sheets.Stem cell research & therapy · 2025Article
- Induced Pluripotent (iPSC) and Mesenchymal (MSC) Stem Cells for In Vitro Disease Modeling and Regenerative Medicine.International journal of molecular sciences · 2025Review
- Dissecting endothelial cell heterogeneity with new tools.Cell regeneration (London, England) · 2025Review
- Human iPSC-based disease modeling studies identify a common mechanistic defect and potential therapies for AMD and related macular dystrophies.Developmental cell · 2024Article
- Genetic and Cellular Basis of Impaired Phagocytosis and Photoreceptor Degeneration in CLN3 Disease.Investigative ophthalmology & visual science · 2024Article
- Advances in retinal pigment epithelial cell transplantation for retinal degenerative diseases.Stem cell research & therapy · 2024Review
- Tissue Engineering of Outer Blood Retina Barrier for Therapeutic Development.Current opinion in biomedical engineering · 2024Article
- Aging of the eye: Lessons from cataracts and age-related macular degeneration.Ageing research reviews · 2024Review
- Establishment of an in vitro choroid complex system for vascular response screening.Scientific reports · 2024Article
- Exosomes secreted from induced pluripotent stem cell ameliorate the lipopolysaccharide induced neuroinflammatory response via lncRNA-0949.Immunity, inflammation and disease · 2024Article
- Advances in the engineering of the outer blood-retina barrier: From in-vitro modelling to cellular therapy.Bioactive materials · 2024Review
- Acute and continuous exposure of airborne fine particulate matter (PMParticle and fibre toxicology · 2023Article
- Mechanism of piR-1245/PIWI-like protein-2 regulating Janus kinase-2/signal transducer and activator of transcription-3/vascular endothelial growth factor signaling pathway in retinal neovascularization.Neural regeneration research · 2023Article
- Deglycosylation Increases the Aggregation and Angiogenic Properties of Mutant Tissue Inhibitor of Metalloproteinase 3 Protein: Implications for Sorsby Fundus Dystrophy.International journal of molecular sciences · 2022Article
- The Essential Role of the Choriocapillaris in Vision: Novel Insights from Imaging and Molecular Biology.Annual review of vision science · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 3 institutions in 1 country.
Kannan V ManianDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA.
Chad A GallowayDepartment 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.
Sonal DalviDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA.
Anthony A EmanuelDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA.
Jared A MerenessDepartment 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.
Whitney BlackDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA.
Lauren WinschelDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA.
Celia SotoDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Department of Biomedical Genetics, University of Rochester, Rochester, NY 14620, USA.
Yiming LiDepartment of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA.
Yuanhui SongDepartment of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA.
William DeMariaDepartment of Biomedical Engineering, Robert B. Goergen Hall, University of Rochester, Rochester, NY 14627, USA.
Akhilesh KumarWisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA.
Igor SlukvinWisconsin 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.
Michael P SchwartzNSF 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.
William L MurphyDepartment of Biomedical Engineering, University of Wisconsin, Madison, WI 53715, USA; Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, WI 53715, USA.
Bela Anand-ApteDepartment of Ophthalmic Research, Cole Eye Institute and Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
Mina ChungDepartment of Ophthalmology, University of Rochester, Rochester, NY 14620, USA; Center for Visual Science, University of Rochester, Rochester, NY 14620, USA.
Danielle S W BenoitDepartment 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.
Ruchira SinghDepartment 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.
University of Rochester · USUniversity of Wisconsin–Madison · USCleveland Clinic Lerner College of Medicine · US
Funding
Training in Environment ToxicologyT32ES007026 · NIEHS · UNIVERSITY OF ROCHESTER · PI Alison Elder, Marissa Sobolewski Terry · 1985 to 2026
$20.2MRESOURCE/SERVICE CORE C - MOLECULAR INFORMATICS MODULEP30EY025585 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI BELA ANAND-APTE · 2016 to 2026
$7.7MTissue Engineering Strategies to Revitalize Bone AllograftsR01AR064200 · NIAMS · UNIVERSITY OF ROCHESTER · PI Danielle S. Benoit · 2013 to 2026
$4.0MRegulation of Choroidal Neovascularization in Sorsby's Fundus DystrophyR01EY027083 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI ANAND-APTE, BELA · 2017 to 2024
$4.0MDelineating the role of TIMP3 in macular degenerationR01EY028167 · NEI · UNIVERSITY OF ROCHESTER · PI SINGH, RUCHIRA · 2017 to 2025
$3.8MRole of Retinoic Acid in the Regulation of the Blood-Retinal Barrier.R01EY026181 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI ANAND-APTE, BELA · 2016 to 2020
$2.1MRPE, aging and age-related macular degeneration: the role of oxidative stressR01EY027750 · NEI · CLEVELAND CLINIC LERNER COM-CWRU · PI BONILHA, VERA L · 2017 to 2021
$2.0MDetermining the role of CLN3 in the eyeR01EY030183 · NEI · UNIVERSITY OF ROCHESTER · PI SINGH, RUCHIRA · 2019 to 2022
$2.0MA Neurovascular Microphysiological SystemR01NS109427 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI MURPHY, WILLIAM L. · 2019 to 2023
$1.7MhiPSC-derived tissue mimetics of the retina blood barrierR21EY030817 · NEI · UNIVERSITY OF ROCHESTER · PI BENOIT, DANIELLE S., SINGH, RUCHIRA · 2020 to 2021
$417kNEI NIH HHS P30 EY025585NEI NIH HHS R01 EY026181NEI NIH HHS R01 EY027083NEI NIH HHS R01 EY027750NEI NIH HHS R01 EY028167NEI NIH HHS R01 EY030183NEI NIH HHS R21 EY030817NIAMS NIH HHS R01 AR064200NIEHS NIH HHS T32 ES007026NINDS NIH HHS R01 NS109427
Abstract
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.
Indexed as
Choroid DiseasesInduced Pluripotent Stem CellsMacular DegenerationChoroidHumansRetinal Pigment Epitheliumage-related macular degenerationchoriocapillarischoroidal neovascularizationhydrogelinduced pluripotent stem cellmacular dystrophyretinal pigment epitheliumSorsby's fundus dystrophytissue engineering
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