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Alex W Hewitt, Vikrant Singh, Vania Januar, Alexandra Sexton-Oates, Jamie E Craig, Richard Saffery; Differences in epigenetic age of ocular tissue and the implications for eye disease.. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1845.
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© ARVO (1962-2015); The Authors (2016-present)
A distinct methylation signature has recently been found to tightly correlate with biological age, and accelerated epigenetic ageing has subsequently been implicated in disease. The aim of this work was to determine the epigenetic age of discrete ocular tissue and whole blood from individuals.
This study was approved by the human research ethics committee of the University of the Western Australia (RA/4/1/4805). Whole blood from the subclavian vein and whole eyes was obtained post-mortem. Specimens were taken from the eight donors (all male) with no known ophthalmic disease. Dissected ocular tissue was stored in QIAGEN Allprotect Tissue Reagent (QIAGEN, Hiden, Germany) and DNA extraction was subsequently performed using the QIAGEN DNeasy Blood & Tissue Kit (QIAGEN). Following bisulfite conversion using the Methyleasy bisulfite modification kit, samples were hybridized to Illumina Infinium HumanMethylation450 (Illumina Inc, San Diego, CA, USA) BeadChips (HM450K) according to the manufacturer's protocols. Beta values were extracted using the minfi package in R. Following pre-processing and normalization DNA methylation age was calculated using the algorithms as described by Horvath (Genome Biol, 2013. 14: p. R115)
Specimens from eight males, who had a mean (SD) chronological age of 60.6 (11.3) years, were collected and processed. A linear relationship between the DNA methylation age and chronological age in blood and ocular tissues was identified (r2= 0.37; p=0.048). The epigenetic age of blood samples were found to have the closest correlation to chronological age across all subjects, whilst the neurosensory retina was found to differ the most, with a mean DNA methylation age across individulas of only 16.1 years (r2=0.93, p<0.001). The DNA methylation age of the RPE/Choroid and optic nerve were also found to differ from the chronological age of subjects. Medical comorbidities, preservation interval time or cause of mortality did not appear to influence or account for the difference in epigenetic and chronological age across tissues.
Overall we identified clear differences between the chronological and epigenetic age of ocular tissue. Although the biological reason underlying this observation is not known, our findings may have important implications for age-related eye diseases, which may manifest in part due to an accelerated epigenetic ageing.
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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