Loss of mitochondrial DNA helicase in retinal macroglia drives neovascular retinopathy.
Overview
- Stem Cells and Metabolism, Research Programs Unit, Faculty of Medicine, University of Helsinki,Helsinki, Finland
- Wihuri Research Institute and Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki,Helsinki, Finland
- Institute of Neurosciences, Universitat Autònoma de Barcelona,Bellaterra, Spain
- Department of Cellular Biology, Physiology and Immunology, Animal Physiology Unit, Faculty of Biosciences, Universitat Autònoma de Barcelona,Bellaterra, Spain
- Center for Translational Neuromedicine, University of Copenhagen,Copenhagen, Denmark
- Department of Neurosurgery, Center for Translational Neuromedicine, University of Rochester Medical Center,Rochester, NY USA
- Molecular and Integrative Biosciences Research Programme, University of Helsinki,Helsinki, Finland
- Department of Neuroscience and Biomedical Engineering, Aalto University,Espoo, Finland
- Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki,Helsinki, Finland
- HUS Diagnostic Center, Helsinki University Hospital,Helsinki, Finland
- HiLife, University of Helsinki,Helsinki, Finland
Abstract
Retinopathy is a common symptom in mitochondrial diseases, and a leading cause of blindness in working-age individuals, often arising as a consequence of diabetes. Here, we demonstrate that postnatal loss of the replicative helicase of mitochondrial DNA in the astrocytes and Müller glia induces neovascular retinopathy. In these retinas, the macroglia show pathological reactivation, leading to hallmark features of neovascularization with blood-retina-barrier leakage, secondary microgliosis, and complement cascade activation. Similar reactivation of astrocytes in the cerebral cortex does not compromise vascular integrity, indicating tissue-specific roles of mitochondrial metabolism in macroglia for vascular homeostasis. Three secreted angiogenic factors—Fgf2, Pgf, and Lcn2—known to contribute to diabetic retinopathy, were induced. Spike recordings of the most sensitive retinal ganglion cells revealed normal rod function and intact retinal coding. These findings highlight the critical role of glial mitochondrial metabolism in neovascular retinopathy, with important implications for therapy development for mitochondrial and common forms of vision loss.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- arrayexpress:E-MTAB-9061
, at ArrayExpress; found in the text, “Reanalysis of previously published single-cell…” - geo:GSE63472, at NCBI GEO; found in the text, “Innate immune activation and neuroinflammation…”
Other data links
- ebi.ac.uk/
biostudies/ , EMBL-EBI; found in the notessourcedata
Data availability
The sequencing data generated in this study have been deposited in the European Nucleotide Archive (ENA) and are available under the accession number PRJEB83104 (https://
The source data of this paper are collected in the following database record: biostudies:S-SCDT-10_103
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 28 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 14 authors, 2 keywords, 11 MeSH terms, 18 funders, 69 references.
Cite
This paper
Olander, S., Karaman, S., Suomi, F., Aguilar, K., Zhaivoron, A., Nedergaard, M., Smeds, L., Tiihonen, J., Quintana, A., Hidalgo, J., Alitalo, K., Ala-Laurila, P., Ince-Dunn, G., & Suomalainen, A. (2026). Loss of mitochondrial DNA helicase in retinal macroglia drives neovascular retinopathy. EMBO molecular medicine, 18(7), 2573-2598. https://
BibTeX
@article{olander2026loss
author = {Olander, Sofiia and Karaman, Sinem and Suomi, Fumi and Aguilar, Kevin and Zhaivoron, Aleksandra and Nedergaard, Maiken and Smeds, Lina and Tiihonen, Jussi and Quintana, Albert and Hidalgo, Juan and Alitalo, Kari and Ala-Laurila, Petri and Ince-Dunn, Gulayse and Suomalainen, Anu},
title = {{Loss of mitochondrial DNA helicase in retinal macroglia drives neovascular retinopathy}},
journal = {EMBO molecular medicine},
year = {2026},
month = may,
volume = {18},
number = {7},
pages = {2573--2598},
publisher = {Nature Publishing Group},
issn = {1757-4676},
doi = {10.1038/
url = {https://
pmid = {42103933},
pmcid = {PMC13365537}
}
RIS
TY - JOUR
AU - Olander, Sofiia
AU - Karaman, Sinem
AU - Suomi, Fumi
AU - Aguilar, Kevin
AU - Zhaivoron, Aleksandra
AU - Nedergaard, Maiken
AU - Smeds, Lina
AU - Tiihonen, Jussi
AU - Quintana, Albert
AU - Hidalgo, Juan
AU - Alitalo, Kari
AU - Ala-Laurila, Petri
AU - Ince-Dunn, Gulayse
AU - Suomalainen, Anu
TI - Loss of mitochondrial DNA helicase in retinal macroglia drives neovascular retinopathy
T2 - EMBO molecular medicine
J2 - EMBO Mol Med
PY - 2026
DA - 2026/
VL - 18
IS - 7
SP - 2573
EP - 2598
SN - 1757-4676
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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