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To understand the physiological and molecular impact of ageing on retinal homeostasis, we used the short\u2010lived African turquoise killifish, a model known to naturally develop central nervous system (CNS) ageing hallmarks and vision loss. Bulk and single\u2010cell RNA\u2010sequencing (scRNAseq) of three age groups (6\u2010, 12\u2010, and 18\u2010week\u2010old) identified transcriptional ageing fingerprints in the killifish retina, unveiling pathways also identified in the aged brain, including oxidative stress, gliosis, and inflammageing. These findings were comparable to observations in the ageing mouse retina. Additionally, transcriptional changes in genes related to retinal diseases, such as glaucoma and age\u2010related macular degeneration, were observed. The cellular heterogeneity in the killifish retina was characterized, confirming the presence of all typical vertebrate retinal cell types. Data integration from age\u2010matched samples between the bulk and scRNAseq experiments revealed a loss of cellular specificity in gene expression upon ageing, suggesting potential disruption in transcriptional homeostasis. Differential expression analysis within the identified cell types highlighted the role of glial\/immune cells as important stress regulators during ageing. Our work emphasizes the value of the fast\u2010ageing killifish in elucidating molecular signatures in age\u2010associated retinal disease and vision decline. This study contributes to the understanding of how age\u2010related changes in molecular pathways may impact CNS health, providing insights that may inform future therapeutic strategies for age\u2010related pathologies.<\/jats:p>","DOI":"10.1111\/acel.14192","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T09:23:05Z","timestamp":1715678585000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Age\u2010related dysregulation of the retinal transcriptome in African turquoise killifish"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-8484","authenticated-orcid":false,"given":"Steven","family":"Bergmans","sequence":"first","affiliation":[{"name":"Department of Biology, Animal Physiology and Neurobiology Division, Neural Circuit Development &amp; Regeneration Research Group KU Leuven, Leuven Brain Institute  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9094-6745","authenticated-orcid":false,"given":"Nicole C. 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