Evidence map›Paper›PMID 34911940›Full record

ArticleNature communications2021

Epithelial phenotype restoring drugs suppress macular degeneration phenotypes in an iPSC model.

Ruchi Sharma, Aman George, Malika Nimmagadda, Davide Ortolan, Barbosa-Sabanero Karla, Zoya Qureshy, Devika Bose, Roba Dejene, Genqing Liang, Qin Wan and 13 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed, 1 pooled it
9.0field-weighted citation impact, top 1% 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

43 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

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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

23 authors at 1 institution in 1 country.

Ruchi SharmaOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Aman George *Pediatric, Developmental, & Genetic Ophthalmology Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Malika Nimmagadda *Ocular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Davide OrtolanOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-8236-9391
Barbosa-Sabanero KarlaOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-9259-2861
Zoya QureshyOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Devika BoseOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Roba DejeneOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Genqing LiangOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Qin WanOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Justin ChangOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Balendu Shekhar JhaOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-6509-8171
Omar MemonOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Kiyoharu Joshua MiyagishimaOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-9744-3152
Aaron RisingOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Madhu LalResearch Governance Council, FDA, White Oak, MD, USA.
Eric HansonIntramural Research Program, NIAMS, National Institutes of Health, Bethesda, MD, 20892, USA.
Rebecca KingDivision of Preclinical Innovation, NCATS, National Institutes of Health, Rockville, MD, 20850, USA.
Mercedes Maria CamposHistology Core, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Marc FerrerDivision of Preclinical Innovation, NCATS, National Institutes of Health, Rockville, MD, 20850, USA.
Juan AmaralOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
David McGaugheyOphthalmic Genetics and Visual Functions Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Kapil BhartiOcular and Stem Cell Translational Research Section, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Kapil.Bharti@nih.gov.ORCID http://orcid.org/0000-0003-4884-3173
National Institutes of Health · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Age-related Macular Degeneration (AMD), a blinding eye disease, is characterized by pathological protein- and lipid-rich drusen deposits underneath the retinal pigment epithelium (RPE) and atrophy of the RPE monolayer in advanced disease stages - leading to photoreceptor cell death and vision loss. Currently, there are no drugs that stop drusen formation or RPE atrophy in AMD. Here we provide an iPSC-RPE AMD model that recapitulates drusen and RPE atrophy. Drusen deposition is dependent on AMD-risk-allele CFH(H/H) and anaphylatoxin triggered alternate complement signaling via the activation of NF-κB and downregulation of autophagy pathways. Through high-throughput screening we identify two drugs, L-745,870, a dopamine receptor antagonist, and aminocaproic acid, a protease inhibitor that reduce drusen deposits and restore RPE epithelial phenotype in anaphylatoxin challenged iPSC-RPE with or without the CFH(H/H) genotype. This comprehensive iPSC-RPE model replicates key AMD phenotypes, provides molecular insight into the role of CFH(H/H) risk-allele in AMD, and discovers two candidate drugs to treat AMD.

Indexed as

AllelesAminocaproic AcidComplement Factor HDrug Evaluation, PreclinicalHumansInduced Pluripotent Stem CellsMacular DegenerationModels, BiologicalPhenotypePyridinesPyrrolesRetinal Pigment Epithelium3-((4-(4-chlorophenyl)piperazin-1-yl)methyl)-1H-pyrrolo(2,3-b)pyridineAminocaproic AcidCFH protein, humanComplement Factor HPyridinesPyrroles

Identifiers

PMID34911940
PMCPMC8674335
OpenAlexW4200029988

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.