Evidence map›Paper›PMID 31840941›Full record

ArticleStem cells translational medicine2020

Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions.

Jie Gong, Hui Cai, NYSCF Global Stem Cell Array Team, Scott Noggle, Daniel Paull, Lawrence J Rizzolo, Lucian V Del Priore, Mark A Fields

Open access · goldAbstract read
In one paragraph

Article in Stem cells translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 51 citations in OpenAlex.

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  7. Molecular and cellular imaging of the eye.Biomedical optics express · 2024
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  9. The interactions betweenMolecular vision · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Jie GongDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut.
Hui CaiDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut.
NYSCF Global Stem Cell Array TeamThe New York Stem Cell Foundation (NYSCF) Research Institute, New York, New York.
Scott NoggleThe New York Stem Cell Foundation (NYSCF) Research Institute, New York, New York.
Daniel PaullThe New York Stem Cell Foundation (NYSCF) Research Institute, New York, New York.
Lawrence J RizzoloDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut.
Lucian V Del PrioreDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut.
Mark A FieldsDepartment of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut.ORCID 0000-0002-0185-0969
Yale University · USNew York Stem Cell Foundation · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Core Grant for Vision ResearchP30EY026878 · NEI · YALE UNIVERSITY · PI In-Jung Kim · 2016 to 2026
$7.1M
NCATS NIH HHS UL1 TR001863NEI NIH HHS P30 EY026878
6 · The paper itself

Abstract

Modeling age-related macular degeneration (AMD) is challenging, because it is a multifactorial disease. To focus on interactions between the retinal pigment epithelium (RPE) and Bruch's membrane, we generated RPE from AMD patients and used an altered extracellular matrix (ECM) that models aged Bruch's membrane. Induced pluripotent stem cells (iPSCs) were generated from fibroblasts isolated from AMD patients or age-matched (normal) controls. RPE derived from iPSCs were analyzed by morphology, marker expression, transepithelial electrical resistance (TER), and phagocytosis of rod photoreceptor outer segments. Cell attachment and viability was tested on nitrite-modified ECM, a typical modification of aged Bruch's membrane. DNA microarrays with hierarchical clustering and analysis of mitochondrial function were used to elucidate possible mechanisms for the observed phenotypes. Differentiated RPE displayed cell-specific morphology and markers. The TER and phagocytic capacity were similar among iPSC-derived RPE cultures. However, distinct clusters were found for the transcriptomes of AMD and control iPSC-derived RPE. AMD-derived iPSC-RPE downregulated genes responsible for metabolic-related pathways and cell attachment. AMD-derived iPSC-RPE exhibited reduced mitochondrial respiration and ability to attach and survive on nitrite-modified ECM. Cells that did attach induced the expression of complement genes. Despite reprogramming, iPSC derived from AMD patients yielded RPE with a transcriptome that is distinct from that of age-matched controls. When challenged with an AMD-like modification of Bruch's membrane, AMD-derived iPSC-RPE activated the complement immune system.

Indexed as

Bruch MembraneHumansInduced Pluripotent Stem CellsMacular DegenerationRetinal Pigment Epitheliumage-related macular degenerationagingBruch's membraneinduced pluripotent stem cellsnonenzymatic nitrationretinal pigment epithelium

Identifiers

PMID31840941
PMCPMC7031648
OpenAlexW2995122020

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.