June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Transcriptional and DNA methylation changes during aging in rod photoreceptors
Author Affiliations & Notes
  • Ximena Corso Diaz
    NNRL, National Eye Institute, NIH, Bethesda, Maryland, United States
  • Freekje Van Asten
    NNRL, National Eye Institute, NIH, Bethesda, Maryland, United States
  • Tiziana Cogliati
    NNRL, National Eye Institute, NIH, Bethesda, Maryland, United States
  • Jennifer Joanna Barb
    Mathematical and Statistical Computing Laboratory, Center for Information Technology, NIH, Bethesda, Maryland, United States
  • Norimoto Gotoh
    NNRL, National Eye Institute, NIH, Bethesda, Maryland, United States
  • Matthew Brooks
    NNRL, National Eye Institute, NIH, Bethesda, Maryland, United States
  • Anand Swaroop
    NNRL, National Eye Institute, NIH, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Ximena Corso Diaz, None; Freekje Van Asten, None; Tiziana Cogliati, None; Jennifer Barb, None; Norimoto Gotoh, None; Matthew Brooks, None; Anand Swaroop, None
  • Footnotes
    Support  National Eye Institute Intramural Research Program
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1844. doi:
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      Ximena Corso Diaz, Freekje Van Asten, Tiziana Cogliati, Jennifer Joanna Barb, Norimoto Gotoh, Matthew Brooks, Anand Swaroop; Transcriptional and DNA methylation changes during aging in rod photoreceptors. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1844.

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

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Abstract

Purpose : The contribution of DNA methylation changes during aging to functional decline and disease is poorly understood. To unravel the mechanistic relationship between age-specific DNA methylation changes and disease in the retina, a correlation between DNA methylation and gene expression in individual retinal cell-types is necessary. Here, we aim to study the transcriptional and DNA methylation changes in rod photoreceptors during aging and the nature of their correlation.

Methods : RNA and DNA were isolated from flow-sorted rod photoreceptors collected from male mice at four time-points: 3M, 12M, 18M and 24M (N=3). RNA-Seq was used to study the transcriptional landscape during aging. A bioinformatics pipeline was implemented to assess changes in gene expression. A list of differentially expressed genes was compiled using 20% FDR cut-off, and validated by RT-PCR. Whole-genome bisulfite sequencing (>10X coverage) was performed to assess DNA methylation levels followed by computational analysis.

Results : Changes in the expression of genes involved in mitochondrial oxidative metabolism, protein degradation and pathways converging on Stat3-dependent signaling were observed in isolated rods during aging. Similar levels of global methylation, including high levels of methylation in the non-CpG context, were observed in all ages. Twenty-four month old rods exhibited high variability in their methylation pattern with several genes displaying differentially methylated regions compared to three-month-old rods. We are currently pursuing a comprehensive analysis of differentially methylated regions in the CpG and non-CpG context for all ages and their correlation with transcriptional changes.

Conclusions : This study unravels candidate mechanisms of photoreceptor aging and will shed light into the functional consequences of age-dependent DNA methylation changes in rods.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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