Evidence map›Paper›PMID 36899910›Full record

ArticleCells2023

Zinc Supplementation Induced Transcriptional Changes in Primary Human Retinal Pigment Epithelium: A Single-Cell RNA Sequencing Study to Understand Age-Related Macular Degeneration.

Eszter Emri, Oisin Cappa, Caoimhe Kelly, Elod Kortvely, John Paul SanGiovanni, Brian S McKay, Arthur A Bergen, David A Simpson, Imre Lengyel

Open access · goldFull text read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 34% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. [Retinal protective effects of zincZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025
    Article
  2. Article
  3. Article
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

9 authors at 4 institutions in 4 countries.

Eszter EmriWellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast BT97BL, UK.
Oisin CappaWellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast BT97BL, UK.ORCID 0000-0002-3015-3345
Caoimhe KellyWellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast BT97BL, UK.
Elod KortvelyImmunology, Infectious Diseases and Ophthalmology (I2O) Discovery and Translational Area, Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.ORCID 0000-0003-1599-3116
John Paul SanGiovanniBiosciences Research Laboratories, BIO5 Institute, University of Arizona, 1230 North Cherry Avenue, Tucson, AZ 85724, USA.
Brian S McKayDepartment of Ophthalmology and Vision Science, University of Arizona, 1656 E. Mabel Street, Tucson, AZ 85724, USA.
Arthur A BergenSection Ophthalmogenetics, Department of Human Genetics, Queen Emma Centre for Precision Medicine, Amsterdam UMC, Location AMC, 1105AZ Amsterdam, The Netherlands.
David A SimpsonWellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast BT97BL, UK.ORCID 0000-0003-0157-1211
Imre LengyelWellcome-Wolfson Institute for Experimental Medicine, Queen's University of Belfast, Belfast BT97BL, UK.ORCID 0000-0001-7467-2174
Queen's University Belfast · GBUniversity of Arizona · USNetherlands Institute for Neuroscience · NLRoche (Switzerland) · CH

Funding

British Heart Foundation FS/19/28/34358
6 · The paper itself

Abstract

Zinc supplementation has been shown to be beneficial to slow the progression of age-related macular degeneration (AMD). However, the molecular mechanism underpinning this benefit is not well understood. This study used single-cell RNA sequencing to identify transcriptomic changes induced by zinc supplementation. Human primary retinal pigment epithelial (RPE) cells could mature for up to 19 weeks. After 1 or 18 weeks in culture, we supplemented the culture medium with 125 µM added zinc for one week. RPE cells developed high transepithelial electrical resistance, extensive, but variable pigmentation, and deposited sub-RPE material similar to the hallmark lesions of AMD. Unsupervised cluster analysis of the combined transcriptome of the cells isolated after 2, 9, and 19 weeks in culture showed considerable heterogeneity. Clustering based on 234 pre-selected RPE-specific genes divided the cells into two distinct clusters, we defined as more and less differentiated cells. The proportion of more differentiated cells increased with time in culture, but appreciable numbers of cells remained less differentiated even at 19 weeks. Pseudotemporal ordering identified 537 genes that could be implicated in the dynamics of RPE cell differentiation (FDR < 0.05). Zinc treatment resulted in the differential expression of 281 of these genes (FDR < 0.05). These genes were associated with several biological pathways with modulation of ID1/ID3 transcriptional regulation. Overall, zinc had a multitude of effects on the RPE transcriptome, including several genes involved in pigmentation, complement regulation, mineralization, and cholesterol metabolism processes associated with AMD.

Indexed as

Macular DegenerationRetinal Pigment EpitheliumGene Expression ProfilingHumansSequence Analysis, RNAZincZincage-related macular degenerationmaturationretinal pigment epitheliumsingle-cell RNA sequencingzinc

Identifiers

PMID36899910
PMCPMC10000409
OpenAlexW4322741782

What OpenQuestion holds

Textfull text, public
LicenceCC BY
reference markers read2
measurements read24
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.