Diabetes Reshapes the Circadian Transcriptome Profile in Murine Retina

Oct 3, 2023Investigative ophthalmology & visual science

Diabetes changes daily gene activity patterns in the mouse retina

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Abstract

The retina of diabetic mice showed significant alterations in the circadian transcriptome after 12 weeks of diabetes.

Circadian rhythm alterations in the retina are linked to diabetic retinopathy.
Diabetes modified the transcriptome characteristics of the retina, affecting composition, phase, and amplitude of rhythmic transcripts.
Temporal and clustering enrichment pathways in the retina were reorganized in diabetic mice.
Diabetes may impact the core clock mechanisms in the retina.

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PURPOSE: Diabetic retinopathy (DR) is a common complication of diabetes and has a high prevalence. Dysregulation of circadian rhythmicity is associated with the development of DR. This research aimed to investigate rhythmical transcriptome alterations in the retina of diabetic mice.

METHODS: C57BL/6J mice were used to establish a diabetes model by intraperitoneal injection of streptozotocin (STZ). After 12 weeks, retinas were collected continuously at 4-hour intervals over 1 day. Total RNA was extracted from normal and STZ-treated retinas and RNA sequencing was performed. Meta2d algorithm, Kyoto Encyclopedia of Genes, Phase Set Enrichment Analysis, and time-series cluster analysis were used to identify, analyze and annotate the composition, phase, and molecular functions of rhythmic transcripts in retinas.

RESULTS: The retina exhibited powerful transcriptome rhythmicity. STZ-induced diabetes markedly modified the transcriptome characteristics of the circadian transcriptome in the retina, including composition, phase, and amplitude. Moreover, the diabetic mice led to re-organized temporal and clustering enrichment pathways in space and time and affected core clock machinery.

CONCLUSIONS: Diabetes impairs the circadian rhythm of the transcriptomic profile of retinas. This study offers new perspectives on the negative effects of diabetes on the retina, which may provide important information for the development of new treatments for DR.

Key numbers

1158

Increase in Rhythmic Genes

Number of rhythmic genes unique to diabetic mice.

Lower amplitude

Decrease in Amplitude

Amplitude comparison of rhythmic genes in diabetic vs. normal mice.

Pathways Enriched in Diabetic Retina

Number of significantly enriched pathways in diabetic retinas.

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Diabetes Reshapes the Circadian Transcriptome Profile in Murine Retina

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