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Mapping the daily rhythmic transcriptome in the diabetic retina. | LitMetric

Mapping the daily rhythmic transcriptome in the diabetic retina.

Vision Res

Wellcome Wolfson Institute for Experimental Medicine, Queens' University Belfast, Northern Ireland, United Kingdom. Electronic address:

Published: January 2024

AI Article Synopsis

  • Retinal function undergoes significant changes between day and night, yet most clinical assessments are conducted during the day, creating a knowledge gap in how conditions like diabetes affect daily retinal rhythms.
  • This study focused on diabetic mice and their non-diabetic counterparts, analyzing gene expression patterns in the retina throughout a 24-hour light/dark cycle using mRNA sequencing.
  • The results showed that while the diabetic retina retains a 12-hour rhythmic expression similar to non-diabetic mice, some genes are phase advanced, indicating potential internal desynchrony that might contribute to diabetic retinopathy.

Article Abstract

Retinal function changes dramatically from day to night, yet clinical diagnosis, treatments, and experimental sampling occur during the day. To begin to address this gap in our understanding of disease pathobiology, this study investigates whether diabetes affects the retina's daily rhythm of gene expression. Diabetic, Ins2 mice, and non-diabetic littermates were kept under a 12 h:12 h light/dark cycle until 4 months of age. mRNA sequencing was conducted in retinas collected every 4 h throughout the 24 hr light/dark cycle. Computational approaches were used to detect rhythmicity, predict acrophase, identify differential rhythmic patterns, analyze phase set enrichment, and predict upstream regulators. The retinal transcriptome exhibited a tightly regulated rhythmic expression with a clear 12-hr transcriptional axis. Day-peaking genes were enriched for DNA repair, RNA splicing, and ribosomal protein synthesis, night-peaking genes for metabolic processes and growth factor signaling. Although the 12-hr transcriptional axis is retained in the diabetic retina, it is phase advanced for some genes. Upstream regulator analysis for the phase-shifted genes identified oxygen-sensing mechanisms and HIF1alpha, but not the circadian clock, which remained in phase with the light/dark cycle. We propose a model in which, early in diabetes, the retina is subjected to an internal desynchrony with the circadian clock and its outputs are still light-entrained whereas metabolic pathways related to neuronal dysfunction and hypoxia are phase advanced. Further studies are now required to evaluate the chronic implications of such desynchronization on the development of diabetic retinopathy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11330665PMC
http://dx.doi.org/10.1016/j.visres.2023.108339DOI Listing

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