Evidence map›Paper›PMID 38964324›Full record

ArticleStem cell reports2024

Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation.

Rozaliya Tsikandelova, Eldo Galo, Edvinas Cerniauskas, Dean Hallam, Maria Georgiou, Rodrigo Cerna-Chavez, Robert Atkinson, Pavel Palmowski, Florence Burté, Tracey Davies and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–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

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  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

21 authors.

Rozaliya TsikandelovaBiosciences Institute, Newcastle University, Newcastle, UK.
Eldo GaloBiosciences Institute, Newcastle University, Newcastle, UK.
Edvinas CerniauskasBiosciences Institute, Newcastle University, Newcastle, UK.
Dean HallamBiosciences Institute, Newcastle University, Newcastle, UK.
Maria GeorgiouBiosciences Institute, Newcastle University, Newcastle, UK.
Rodrigo Cerna-ChavezBiosciences Institute, Newcastle University, Newcastle, UK.
Robert AtkinsonBiosciences Institute, Newcastle University, Newcastle, UK.
Pavel PalmowskiBiosciences Institute, Newcastle University, Newcastle, UK.
Florence BurtéBiosciences Institute, Newcastle University, Newcastle, UK.
Tracey DaviesElectron Microscopy Research Services, Newcastle University, Newcastle, UK.
David H SteelBiosciences Institute, Newcastle University, Newcastle, UK.
Martin McKibbinLeeds Teaching Hospitals NHS Trust, Leeds UK and Leeds Institute for Medical Research, St. James's University Hospital, University of Leeds, Leeds, UK.
Jacquelyn BondLeeds Teaching Hospitals NHS Trust, Leeds UK and Leeds Institute for Medical Research, St. James's University Hospital, University of Leeds, Leeds, UK.
Jennifer HaggartyShared Research Facilities, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Phil WhitfieldGlasgow Polyomics and Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Viktor KorolchukBiosciences Institute, Newcastle University, Newcastle, UK.
Lyle ArmstrongBiosciences Institute, Newcastle University, Newcastle, UK.
Chunbo YangBiosciences Institute, Newcastle University, Newcastle, UK.
Birthe DorgauBiosciences Institute, Newcastle University, Newcastle, UK.
Marzena Kurzawa-AkanbiBiosciences Institute, Newcastle University, Newcastle, UK.
Majlinda LakoBiosciences Institute, Newcastle University, Newcastle, UK. Electronic address: majlinda.lako@ncl.ac.uk.

Funding

Medical Research Council MR/X001687/1National Centre for the Replacement, Refinement and Reduction of Animals in Research NC/C016106/1
6 · The paper itself

Abstract

Biallelic mutations in DRAM2 lead to an autosomal recessive cone-rod dystrophy known as CORD21, which typically presents between the third and sixth decades of life. Although DRAM2 localizes to the lysosomes of photoreceptor and retinal pigment epithelium (RPE) cells, its specific role in retinal degeneration has not been fully elucidated. In this study, we generated and characterized retinal organoids (ROs) and RPE cells from induced pluripotent stem cells (iPSCs) derived from two CORD21 patients. Our investigation revealed that CORD21-ROs and RPE cells exhibit abnormalities in lipid metabolism, defects in autophagic flux, accumulation of aberrant lysosomal content, and reduced lysosomal enzyme activity. We identified potential interactions of DRAM2 with vesicular trafficking proteins, suggesting its involvement in this cellular process. These findings collectively suggest that DRAM2 plays a crucial role in maintaining the integrity of photoreceptors and RPE cells by regulating lysosomal function, autophagy, and potentially vesicular trafficking.

Indexed as

AutophagyInduced Pluripotent Stem CellsLysosomesMembrane ProteinsRetinal Pigment EpitheliumCone-Rod DystrophiesHumansLipid MetabolismMutationOrganoidsRetinaDRAM2 protein, humanMembrane ProteinsautophagyCORD21DRAM2lipd metabolismlysosomesretinal organoidsRPE cellsvesicular transport

Identifiers

PMID38964324
PMCPMC11368688

What OpenQuestion holds

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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.