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Lookup NU author(s): Dr Rozaliya Tsikandelova, Eldo Galo, Edvinas Cerniauskas, Dr Dean Hallam, Dr Maria Georgiou, Rodrigo Cerna Chavez, Rob Atkinson, Dr Pawel PalmowskiORCiD, Dr Florence Burté, Professor David SteelORCiD, Professor Viktor KorolchukORCiD, Professor Lyle Armstrong, Dr Chunbo Yang, Dr Marzena Kurzawa-Akanbi, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s)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.
Author(s): Tsikandelova R, Galo E, Cerniauskas E, Hallam D, Georgiou M, Cerna-Chavez R, Atkinson R, Palmowski P, Burte F, Davies T, Steel DH, McKibbin M, Bond J, Haggarty J, Whitfield P, Korolchuk V, Armstrong L, Yang C, Dorgau B, Kurzawa-Akanbi M, Lako M
Publication type: Article
Publication status: Published
Journal: Stem Cell Reports
Year: 2024
Pages: epub ahead of print
Online publication date: 03/07/2024
Acceptance date: 31/05/2024
Date deposited: 29/07/2024
ISSN (electronic): 2213-6711
Publisher: Cell Press
URL: https://doi.org/10.1016/j.stemcr.2024.06.002
DOI: 10.1016/j.stemcr.2024.06.002
Data Access Statement: The proteomics data have been submitted into MassIVE:MSV000094178.
PubMed id: 38964324
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