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oai:figshare.com:article/32633943 2026-10-01T16:59:15Z portal_1172 item_type_8 month_year_10_2026

Identification of age-related changes and intracellular DNA sensors in the retina, using single-cell transcriptomics Miao Tang (3336636) PUREID: 426356550 Ageing DNA sensors single-cell transcriptomics retina Ageing is a major risk factor for developing retinal diseases. Ageing is characterised by a decline in repair and disruption in homeostasis, which is accompanied by changes in transcriptomic and protein expression. The contribution of ageing to retinal diseases remains largely unspecified. We investigated age-related transcriptional changes at the single cell resolution using single-cell transcriptomics. We established a single-cell atlas of the ageing mouse neuroretina. We noticed age-associated cell-type proportion changes characterised by rod loss. We identified age-related, cell-type specific transcriptional changes. Ageing rods have shown metabolic reprogramming, while ageing macroglia have shown a reactive gliosis phenotype. Genomic instability and increased proteostasis burden was found in ageing bipolar cells. Meanwhile, the bidirectional communication between microglia and other retinal cells was also found to be altered in the ageing retina that favours a low-grade chronic inflammation (para-inflammation). To understand how inflammation is initiated in the ageing retina, we focused on retinal DNA sensing pathways. Intracellular DNA sensors initiate the host immune response by recognising cytosolic DNA derived from pathogen replication or endogenous nucleic acid released by damaged nuclei or mitochondria. The retinal DNA sensing system requires further investigation. We established an expression profile of retinal intracellular DNA sensors. We further confirmed the expression of the adaptor protein of DNA sensing pathway, STING, in the retina. We demonstrated that STING is critically involved in dsDNA-induced type I IFN response in microglia and RPE cells, but not in photoreceptors and Müller glia. An increased enrichment of DNA sensors was detected in microglia in the ageing retina. Significant increase of Sting expression was found in the ageing mouse neuroretina. Studies have suggested the DNA sensing pathways connects genomic instability and inflammation during ageing. These results suggest that DNA sensors activation may be partially responsible for para-inflammation in the ageing retina.<br><br><i>Thesis is embargoed until 31 July 2028</i>.<br><br> 2026-10-01T16:59:15Z Text Thesis 10.17034/32633943.v1 https://figshare.com/articles/thesis/Identification_of_age-related_changes_and_intracellular_DNA_sensors_in_the_retina_using_single-cell_transcriptomics/32633943 All Rights Reserved Open Access after 2028-07-31