Evidence map›Paper›PMID 42106786›Full record

ArticleGenome medicine2026

Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration.

Jenna C Hall, Kavitha Krishna Sudhakar, Maciej Daniszewski, Anne Senabouth, Carla J Abbott, Helena H Liang, Himeesh Kumar, Grace E Lidgerwood, Mehdi Mirzaei, Jessica Yw Ma and 17 more

Erratum issuedAbstract read
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In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors.

Jenna C Hall *Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Kavitha Krishna Sudhakar *Translational Genomics, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Maciej Daniszewski *Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Anne Senabouth *Translational Genomics, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Carla J AbbottCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia.
Helena H LiangCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia.
Himeesh KumarCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia.
Grace E LidgerwoodDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Mehdi MirzaeiFaculty of Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney, NSW, 2109, Australia.
Jessica Yw MaDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Trevor AtkesonTranslational Genomics, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Yumiko HirokawaDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Emeline F NandrotSorbonne Université, CNRS, INSERM, Institut de La Vision, Paris, 75012, France.
Alexander BarnettMenzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 7000, Australia.
Chantal CazevieilleUniversité de Montpellier, INSERM U1298, Institut Des Neurosciences de Montpellier, Hôpital Saint-Eloi, Montpellier, France.
Gaël ManesUniversité de Montpellier, INSERM U1298, Institut Des Neurosciences de Montpellier, Hôpital Saint-Eloi, Montpellier, France.
Simon MountfordMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3058, Australia.
Philip ThompsonMonash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3058, Australia.
Erica L FletcherDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia.
Zhichao WuCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia.
Melanie BahloPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3010, Australia.
Brendan R E AnsellPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3010, Australia.
Daniel PaullThe New York Stem Cell Foundation Research Institute, New York, USA.
Alex W Hewitt *Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia.
Robyn H Guymer *Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, 3002, Australia.
Joseph E Powell *Translational Genomics, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Alice Pébay *Department of Anatomy and Physiology, The University of Melbourne, Parkville, VIC, 3010, Australia. apebay@unimelb.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAge-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.

methodsWe generated induced pluripotent stem cell-derived RPE cells from a clinically phenotyped cohort comprising only individuals with conventional drusen (AMD/RPD-) or with drusen coexisting with RPD (AMD/RPD +). To identify differences between the two cohorts, we performed single-cell transcriptomic, proteomic, quantitative trait locus (QTL) and transcriptome-wide association (TWAS) analyses, together with functional assays.

resultsAMD/RPD + RPE cells exhibited enrichment of extracellular matrix (ECM) and hypoxia-responsive pathways, and a relative underrepresentation of mitochondrial and oxidative phosphorylation processes, when compared with AMD/RPD- cells. Genetic analyses supported shared modulation of mitochondrial pathways across AMD, with additional regulatory signals associated with RPD risk. Functionally, all RPE cohorts formed drusen-like deposits in vitro. AMD/RPD- lines generated more basal deposits, whereas AMD/RPD + cells exhibited increased susceptibility to monolayer disruption.

conclusionsThese 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.

Indexed as

Induced Pluripotent Stem CellsMacular DegenerationRetinal DrusenExtracellular MatrixGene Expression ProfilingHumansMitochondriaPhenotypeProteomicsQuantitative Trait LociRetinal Pigment EpitheliumTranscriptomeAge-related macular degenerationGenome regulationHuman induced pluripotent stem cellsProteomicsReticular pseudodrusenRetinal pigment epitheliumSingle-cell RNA sequencingTranscriptomics

Identifiers

PMID42106786
PMCPMC13157670

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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.