Tsikandelova, R., Galo, E., Cerniauskas, E. et al. (18 more authors) (2024) Retinal cells derived from patients with DRAM2-dependent CORD21 dystrophy exhibit key lysosomal enzyme deficiency and lysosomal content accumulation. Stem Cell Reports, 19 (8). pp. 1107-1121. ISSN 2213-6711
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
Keywords: | DRAM2; CORD21; lysosomes; vesicular transport; autophagy; retinal organoids; RPE cells; lipd metabolism |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 14 Mar 2025 10:22 |
Last Modified: | 14 Mar 2025 10:22 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.stemcr.2024.06.002 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224395 |