April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Hyperhydroxymethylation in rd1 retinal degeneration
Author Affiliations & Notes
  • Arshan Perera
    Department of Pharmacology, LMU Munich, Munich, Germany
  • Susanne Koch
    Department of Pharmacology, LMU Munich, Munich, Germany
  • Martin Biel
    Department of Pharmacology, LMU Munich, Munich, Germany
  • Stylianos Michalakis
    Department of Pharmacology, LMU Munich, Munich, Germany
  • Footnotes
    Commercial Relationships Arshan Perera, None; Susanne Koch, None; Martin Biel, None; Stylianos Michalakis, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5000. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Arshan Perera, Susanne Koch, Martin Biel, Stylianos Michalakis; Hyperhydroxymethylation in rd1 retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5000.

      Download citation file:

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

  • Supplements

Purpose: The removal of DNA methylation in neurons via hydroxylation of Tet enzymes has been implicated in gene regulation and active DNA demethylation. Although, recent studies suggest that DNA methylation is crucial for cell homeostasis, the exact mechanisms how DNA methylation contributes to cell death are still unknown. Here, we investigated the role of 5hmC during retinal degeneration in rd1 mice.

Methods: We labelled and quantified 5hmC and TdT-mediated dUTP-biotin nick end labeling (TUNEL) positive rod photoreceptors in rd1 mice using immunohistochemistry. Next, we mapped 5hmC marks to the retinal genome by hydroxymethylated DNA immunoprecipitation (hMeDIP) followed by next generation sequencing (NGS) in rd1 and wildtype mice. Finally, we performed a correlation analysis of 5hmC-enriched genes in rd1 mice with microarray gene expression data.

Results: At the peak time points of rod photoreceptor degeneration in rd1 mice, we detected elevated levels of 5hmC in rod photoreceptors. Interestingly, we detected a positive correlation of TUNEL positive rod photoreceptors and increased 5hmC levels. The hMeDIP data revealed an acquisition of 5hmC at gene-rich regions. Moreover, gene ontology analysis showed that 5hmC-enriched genes are involved in neurological diseases. Correlation of our hMeDIP data with microarray data revealed that hyperhydroxymethylation in the rd1 retina was accompanied with increased gene expression of the corresponding genes.

Conclusions: Our findings show that 5hmC is enriched in degenerating rod photoreceptors and may contribute to an epigenetically programmed cell death pathway via target activation of cell death-related genes. In summary, our data provide novel insights into the role of 5hmC as an epigenetic regulator during neurodegeneration.

Keywords: 688 retina • 648 photoreceptors • 494 degenerations/dystrophies  

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.