Evidence map›Paper›PMID 41270749›Full record

ArticleStem cell reports2025

Connecting cilium, stress response, and proteostasis abnormalities inform variant and therapy assessment in RPGRIP1 retinal organoids.

To Ha Loi, Anson Cheng, Hani Jieun Kim, Milan Fernando, Benjamin M Nash, Nader Aryamanesh, John R Grigg, Pengyi Yang, Anai Gonzalez-Cordero, Robyn V Jamieson

Abstract read
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In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

10 authors.

To Ha LoiEye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
Anson ChengEye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, University of Sydney, Sydney, NSW, Australia.
Hani Jieun KimComputational Systems Biology Unit, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia; Swarbrick Laboratory, Garvan Institute of Medical Research, The Kinghorn Cancer Centre, Darlinghurst, NSW, Australia.
Milan FernandoStem Cell Medicine Group and Stem Cell and Organoid Facility, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Benjamin M NashEye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, University of Sydney, Sydney, NSW, Australia; Sydney Genome Diagnostics, Western Sydney Genetics Program, Sydney Children's Hospitals Network, Sydney, NSW, Australia; Specialty of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Nader AryamaneshBioinformatics Facility, Children's Medical Research Institute, Sydney, NSW, Australia.
John R GriggEye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, University of Sydney, Sydney, NSW, Australia; Department of Ophthalmology, Sydney Children's Hospitals Network, Sydney, NSW, Australia.
Pengyi YangComputational Systems Biology Unit, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Anai Gonzalez-CorderoStem Cell Medicine Group and Stem Cell and Organoid Facility, Children's Medical Research Institute, University of Sydney, Sydney, NSW, Australia.
Robyn V JamiesonEye Genetics Research Unit, Children's Medical Research Institute, Sydney Children's Hospitals Network, Save Sight Institute, University of Sydney, Sydney, NSW, Australia; Specialty of Genomic Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Department of Clinical Genetics, Western Sydney Genetics Program, Sydney Children's Hospitals Network, Sydney, NSW, Australia. Electronic address: rjamieson@cmri.org.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RPGRIP1 encodes a connecting cilium (CC) protein essential for normal photoreceptor cell development and maintenance. Damaging variants in RPGRIP1 cause severe inherited retinal disease (IRD) and currently incurable vision loss, with mouse studies showing promising preclinical gene augmentation therapy results. Almost one-half of variants in RPGRIP1 in the ClinVar database are variants of uncertain significance (VUS), hindering genetic diagnosis for affected individuals and, hence, access to clinical trials of novel therapies and other management options. Here, we use human induced pluripotent stem cell (iPSC)-derived retinal organoids to model RPGRIP1-associated IRD, detecting biomarkers of disease including CC interactome dysfunction, stress response, and proteostasis abnormalities. In parallel, utilizing these novel disease biomarkers, we demonstrate the pathogenicity of a missense VUS, RPGRIP1 c.2108T>C p.(Ile703Thr). In addition, RPGRIP1 gene augmentation therapy rescued disease phenotypes, further supporting the utility of these biomarkers of RPGRIP1-IRD for reclassifying VUS and testing response to therapy.

Indexed as

Adaptor Proteins, Signal TransducingCiliaOrganoidsProteostasisRetinaRetinal DiseasesStress, PhysiologicalAnimalsBiomarkersCytoskeletal ProteinsHumansInduced Pluripotent Stem CellsMiceAdaptor Proteins, Signal TransducingBiomarkersCytoskeletal ProteinsRPGRIP1 protein, humanAAV therapyciliopathiesgene augmentationinherited retinal diseaseiPSCphotoreceptorsretinal organoidsRPGRIP1transcriptomevariants of uncertain significance

Identifiers

PMID41270749
PMCPMC12744860

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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.