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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. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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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