2026-10-14T09:26:16Z https://api.figshare.com/v2/oai

oai:figshare.com:article/32641617 2026-10-01T16:21:47Z portal_1172 item_type_8 month_year_10_2026

Circadian clocks in diabetes – implications for diabetic retinopathy Hanagh Winter (3740134) PUREID: 651489594 Circadian rhythm diabetic retinopathy endothelial cells diabetes retinopathy retina rhythms chronobiology Circadian Circadian rhythms are intrinsic daily cycles that regulate homeostasis across the body. They are governed by a master clock in the suprachiasmatic nucleus (SCN) and by local tissue clocks, including one in the retina. Unlike most, the retinal clock is independent of the SCN and crucial because it both regulates ocular function and provides light cues that synchronise the master clock. Disturbances in retinal rhythms can therefore affect both eye health and systemic circadian timing. Diabetes, which causes diabetic retinopathy (DR), a leading cause of vision loss, may disrupt these rhythms and in doing so further accelerate retinal pathology.<br><br>This project investigated the bidirectional relationship between circadian rhythms and diabetes using the Ins2Akita mouse model of Type 1 diabetes and human retinal microvascular endothelial cells (HRMECs) exposed to diabetic-like conditions. Approaches included behavioural monitoring, electroretinography, optical coherence tomography, histology, gene expression analysis, and endothelial assays.<br><br>Diabetic mice showed disrupted behavioural rhythms, including increased daytime activity, reduced rhythm amplitude, delayed re-entrainment after jet lag, and heightened sensitivity to dim light. Retinal recordings revealed loss of circadian modulation in photoreceptor and inner retinal responses. Separately, chronic circadian misalignment alone induced retinal thinning, vascular pathology, and impaired rod and cone function. Transcriptomic analysis indicated that circadian misalignment particularly disrupted retinal pigment epithelium function, including extracellular matrix regulation and photoreceptor phagocytosis. In vitro, HRMECs exposed to hyperglycaemia and hypoxia exhibited altered rhythmicity of core circadian genes (Bmal1, Per2), disrupted mitochondrial rhythms, and clock-dependent changes in angiogenic potential.<br><br>Together, these findings show that diabetes disrupts both master and retinal clocks, while circadian misalignment independently drives retinal degeneration. Their combined effects may create a pathological feedback loop that accelerates DR. Protecting circadian rhythms may therefore offer a novel strategy to slow or prevent diabetic retinal disease.<br><br><i>Thesis is embargoed until 31 December 2028.</i> 2026-10-01T16:21:47Z Text Thesis 10.17034/32641617.v1 https://figshare.com/articles/thesis/Circadian_clocks_in_diabetes_implications_for_diabetic_retinopathy/32641617 All Rights Reserved Open Access after 2028-12-31