July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
RNA-seq analysis of retinal pigment epithelium indicates elevated ATP production at a different circadian time point than lipid metabolism
Author Affiliations & Notes
  • Elja Louer
    Ophthalmology, RadboudUMC, Nijmegen, Netherlands
    Physiology, RadboudUMC, Nijmegen, Netherlands
  • Guoqiang Yi
    Molecular biology, Radboud University, Nijmegen, Netherlands
  • Henk Stunnenberg
    Molecular biology, Radboud University, Nijmegen, Netherlands
  • Anneke I Den Hollander
    Ophthalmology, RadboudUMC, Nijmegen, Netherlands
  • Peter Deen
    Physiology, RadboudUMC, Nijmegen, Netherlands
  • Footnotes
    Commercial Relationships   Elja Louer, None; Guoqiang Yi, None; Henk Stunnenberg, None; Anneke Den Hollander, None; Peter Deen, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4917. doi:
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      Elja Louer, Guoqiang Yi, Henk Stunnenberg, Anneke I Den Hollander, Peter Deen; RNA-seq analysis of retinal pigment epithelium indicates elevated ATP production at a different circadian time point than lipid metabolism. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4917.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : The functional interaction between photoreceptor and retinal pigment epithelium (RPE) cells is essential for vision, and decreased interaction is central in age-related macular degeneration (AMD). Phagocytosis of photoreceptor outer segments (POS) by the RPE has a circadian pattern, but it is unknown whether other processes of the RPE follow a circadian rhythm. Disturbed circadian rhythm of cellular processes has been shown to cause age-related diseases. Therefore, our aim was to determine whether and which RPE processes also show a circadian rhythm.

Methods : The physiology of mouse RPE was studied by determining the transcriptome at Zeitgeber time (ZT) 0, 2, 4, 9, 14 and 19 (n=5 per time point). Anterior segments of the eyes were removed and the RPE layer was isolated after which RNA was isolated and sequenced. Genes with a significant difference in expression between time points (DEGs, p<0.05) were identified. EnrichR pathway analysis was used to identify circadian regulated processes.

Results : In total, 756 significant DEGs (p<0.05) were identified. EnrichR pathway enrichment resulted in 13 significantly-enriched KEGG pathways (p<0.01) including circadian rhythm and the metabolic pathway. The metabolic pathway (p= 2,82E-03) showed the highest number of DEGs, being 73. In-depth analysis of these 73 DEGs revealed 2 opposing circadian expression patterns. Genes involved in mitochondrial electron transport showed a high expression at ZT0 and low expression at ZT19, whereas the expression of genes involved in lipid metabolism (e.g. fatty acid degradation, cholesterol synthesis) were low at ZT0 and high at ZT19.

Conclusions : We found that 13 pathways follow a circadian gene expression pattern in RPE cells. In particular, we found that genes involved in mitochondrial electron transport (i.e. ATP generation) and lipid metabolism have opposing expression patterns in RPE cells, of which increase of the latter coincides with POS phagocytosis. These data suggest that the highest energy demand of RPE cells is at another circadian time frame than when POS are phagocytosed. Moreover, because lipid metabolism plays an important role in AMD development, our finding that RPE lipid metabolism is circadian regulated may suggest that RPE cells experience the effect of AMD-associated genetic variants in these genes at particular circadian hours.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.


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