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Alex Hewitt, Jihoon Joo, Jie Wang, Jamie Craig, Richard Saffery; Methylation landscape of ocular tissue and their correlation to peripheral leucocytes. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1739.
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The aim of this study was to investigate the whole genome methylation profiles of ocular tissues. In comparing this profile to unfractionated blood samples from the same individuals, we also sought to investigate the utility of leucocyte DNA methylation in the study of ocular disease.
Whole blood from the subclavian vein and whole eyes (N=##?) were obtained post-mortem. DNA was extracted from whole blood as well as neurosensory retina, retinal pigment epithelium (RPE)/choroid and optic nerve tissue. Following bisulfite conversion samples were hybridized to Illumina Infinium HumanMethylation450 BeadChips according to the manufacture’s protocols. Data were analysed using R v2.15.1.
Following QC a total of 464,993 CpG sites common to all samples were used for subsequent analysis. Unstructured hierarchical clustering of all CpG sites for each sample revealed well-defined groupings across individual tissue subtypes. Despite this discrete clustering, there was generally a strong correlation between methylation profiles, across all tissues from each individual (median (range) Pearsons corr=0.923 (0.851-0.991)). Over 250,000 CpG sites were found to have similar methylation levels (beta <0.2 or beta >0.8) across different tissues in the same individuals, with a further ~18,000 sites having similar methylation profiles in all ocular tissue only.
Our results reveals a strong correlation between the methylation status of peripheral blood leukocytes and different ocular tissues, highlighting the utility of using whole blood to study potential epigenetic changes in ophthalmic disease. These results are particularly encouraging for research where non-end organ tissue is difficult to obtain. An improved understanding of the epigenetic landscape of ocular tissue will have important ramifications for regenerative medicine and ongoing dissection of gene-environment interactions in eye disease.
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