PXD070797-1

PXD070797 is an original dataset announced via ProteomeXchange.

Title	Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration
Description	Age-related macular degeneration (AMD) is a leading cause of vision loss. Reticular pseudodrusen (RPD), deposits on the apical side of the retinal pigment epithelium (RPE), signify a distinctive and critical AMD phenotype. Yet, their molecular basis and relationship to the conventional drusen seen in AMD remain unclear. We generated induced pluripotent stem cell-derived RPE cells from a clinically phenotyped cohort comprising only individuals with conventional drusen (AMD/RPD-) or drusen coexisting with RPD (AMD/RPD+). From these cells, we generated single-cell transcriptomics, proteomics, and functional data to identify differences between the two cohorts. We show that AMD/RPD+ RPE cells exhibit enrichment in extracellular matrix (ECM) remodelling, cytoskeletal, and hypoxia-responsive programs, whereas AMD/RPD- RPE cells display a relatively greater representation of mitochondrial and protein homeostasis pathways. Both subtypes demonstrated molecular hallmarks of ageing, including altered ECM regulation and mitochondrial decline, but differed in the direction and extent of pathway disruption. Expression and protein quantitative trait loci (QTLs) highlight shared genetic influences on mitochondrial and iron-handling pathways, while disease-interacting eQTLs and transcriptome-wide association study identify regulatory signals that are distinctive of the RPD subtype within AMD, including through regulation of ECM. Functionally, all iPSC-derived RPE formed drusen-like deposits in vitro: AMD/RPD- lines generated more basal deposits, whereas AMD/RPD+ cells exhibited greater structural instability under bisretinoid-induced stress. Together, these findings indicate that AMD with and without RPD represent mechanistically distinct entities and provide novel insight into the molecular mechanisms underlying disease heterogeneity in AMD.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_16:37:02.688.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mehdi Mirzaei
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-16 23:37:03	ID requested
⏵ 1	2026-06-07 16:37:03	announced

10.1186/s13073-026-01658-2;

Hall JC, Krishna Sudhakar K, Daniszewski M, Senabouth A, Abbott CJ, Liang HH, Kumar H, Lidgerwood GE, Mirzaei M, Ma JY, Atkeson T, Hirokawa Y, Nandrot EF, Barnett A, Cazevieille C, Manes G, Mountford S, Thompson P, Fletcher EL, Wu Z, Bahlo M, Ansell BRE, Paull D, Hewitt AW, Guymer RH, Powell JE, P, é, bay A, Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration. Genome Med, 18(1):(2026) [pubmed]

submitter keyword: human induced pluripotent stem cells

retinal pigment epithelium

single-cell RNA sequencing

genome regulation

age-related macular degeneration

reticular pseudodrusen

transcriptomics

proteomics.

Alice Pebay
contact affiliation	Dame Kate Campbell Fellow Department of Surgery| Melbourne Medical School Department of Anatomy and Physiology| School of Biomedical Sciences Faculty of Medicine, Dentistry and Health Sciences Medical Building (#181), Grattan Street The University of Melbourne, Victoria 3010 Australia P: +61 3 9035 5464 E: apebay@unimelb.edu.au W: https://medicine.unimelb.edu.au/school-structure/surgery W: https://biomedicalsciences.unimelb.edu.au/departments/anatomy-and-physiology
contact email	apebay@unimelb.edu.au
lab head
Mehdi Mirzaei
contact affiliation	macquarie university
contact email	mehdi.mirzaei@mq.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD070797

PRIDE project URI

• PRIDE
  1. PXD070797
     1. Label: PRIDE project
     2. Name: Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration