Evidence map›Paper›PMID 31332443›Full record

ArticleHuman molecular genetics2019

Regulation of phagolysosomal activity by miR-204 critically influences structure and function of retinal pigment epithelium/retina.

Congxiao Zhang, Kiyoharu J Miyagishima, Lijin Dong, Aaron Rising, Malika Nimmagadda, Genqing Liang, Ruchi Sharma, Roba Dejene, Yuan Wang, Mones Abu-Asab and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.0field-weighted citation impact, top 24% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

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  13. Oxidation of DJ-1 Cysteines in Retinal Pigment Epithelium Function.International journal of molecular sciences · 2022
    Article
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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

16 authors at 2 institutions in 1 country.

Congxiao ZhangOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD USA.
Kiyoharu J MiyagishimaOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD USA.
Lijin DongGenetic Engineering Facility, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Aaron RisingOphthalmic Genetics and Visual Function Branch, Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Malika NimmagaddaOphthalmic Genetics and Visual Function Branch, Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Genqing LiangOphthalmic Genetics and Visual Function Branch, Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Ruchi SharmaOphthalmic Genetics and Visual Function Branch, Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Roba DejeneOphthalmic Genetics and Visual Function Branch, Unit on Ocular and Stem Cell Translational Research, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Yuan WangOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD USA.
Mones Abu-AsabSection of Histopathology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Haohua QianVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Yichao LiVisual Function Core, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Megan KoperaGenetic Engineering Facility, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Arvydas MaminishkisOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD USA.
Jennifer MartinezInflammation and Autoimmunity, National Institute of Environmental Sciences, National Institutes of Health, Bethesda, MD, USA.
Sheldon MillerOphthalmic Genetics and Visual Function Branch, Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, National Institutes of Health, Bethesda, MD USA.
National Institutes of Health · USNational Eye Institute · US

Funding

NEI Genetic Engineering CoreZICEY000458 · NEI · NATIONAL EYE INSTITUTE · PI DONG, LIJIN · 2009 to 2025
$22.6M
Visual Function CoreZICEY000503 · NEI · NATIONAL EYE INSTITUTE · PI QIAN, HAOHUA · 2011 to 2025
$12.3M
Human Retinal Pigment Epithelial PhysiologyZIAEY000419 · NEI · NATIONAL EYE INSTITUTE · PI SCHNEEWEIS, DAVID · 2009 to 2020
$12.0M
Evaluation of Visual Function in Animal ModelsZIAEY000530 · NEI · NATIONAL EYE INSTITUTE · PI QIAN, HAOHUA · 2013 to 2025
$1.8M
6 · The paper itself

Abstract

MicroRNA-204 (miR-204) is expressed in pulmonary, renal, mammary and eye tissue, and its reduction can result in multiple diseases including cancer. We first generated miR-204-/- mice to study the impact of miR-204 loss on retinal and retinal pigment epithelium (RPE) structure and function. The RPE is fundamentally important for maintaining the health and integrity of the retinal photoreceptors. miR-204-/- eyes evidenced areas of hyper-autofluorescence and defective photoreceptor digestion, along with increased microglia migration to the RPE. Migratory Iba1+ microglial cells were localized to the RPE apical surface where they participated in the phagocytosis of photoreceptor outer segments (POSs) and contributed to a persistent build-up of rhodopsin. These structural, molecular and cellular outcomes were accompanied by decreased light-evoked electrical responses from the retina and RPE. In parallel experiments, we suppressed miR-204 expression in primary cultures of human RPE using anti-miR-204. In vitro suppression of miR-204 in human RPE similarly showed abnormal POS clearance and altered expression of autophagy-related proteins and Rab22a, a regulator of endosome maturation. Together, these in vitro and in vivo experiments suggest that the normally high levels of miR-204 in RPE can mitigate disease onset by preventing generation of oxidative stress and inflammation originating from intracellular accumulation of undigested photoreactive POS lipids. More generally, these results implicate RPE miR-204-mediated regulation of autophagy and endolysosomal interaction as a critical determinant of normal RPE/retina structure and function.

Indexed as

AnimalsCells, CulturedChemokinesCytokinesElectrophysiologyFemaleFlow CytometryHumansLysosomal-Associated Membrane Protein 2MaleMiceMice, KnockoutMicroRNAsPhagocytosisPhagosomesRetinaChemokinesCytokinesLysosomal-Associated Membrane Protein 2MicroRNAsMIRN204 microRNA, mouse

Identifiers

PMID31332443
PMCPMC7275778
OpenAlexW2963830789

What OpenQuestion holds

Textmetadata
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.