April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Increased DNA Methylation in Several Animal Models of Retinitis Pigmentosa
Author Affiliations & Notes
  • P. Farinelli
    Ophthalmology, Clinical Sciences, Lund, University of Lund, Lund, Sweden
  • B. Arango-Gonzalez
    Division of Experimental Ophthalmology,
    Centre for Ophthalmology, Tuebingen, Germany
  • J. Kaur
    Division of Ophthalmology,
    Centre for Ophthalmology, Tuebingen, Germany
  • F. Paquet-Durand
    Experimental Ophthalmology, Institute for Ophthalmic Research, Tuebingen, Germany
  • P. A. Ekstrom
    Ophthalmology, Clinical Sci Lund, Lund University, Lund, Sweden
  • Footnotes
    Commercial Relationships  P. Farinelli, None; B. Arango-Gonzalez, None; J. Kaur, None; F. Paquet-Durand, None; P.A. Ekstrom, None.
  • Footnotes
    Support  Swedish Research Council, Medicin; KMA; Torsten och Ragnar Söderbergs Stiftelser; Kerstan Foundation, Stiftelsen f. synskadade i f.d. Malmöhus län
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2234. doi:https://doi.org/
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      P. Farinelli, B. Arango-Gonzalez, J. Kaur, F. Paquet-Durand, P. A. Ekstrom; Increased DNA Methylation in Several Animal Models of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2234. doi: https://doi.org/.

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

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Abstract

Purpose: : Gene repression by DNA methylation is a well documented epigenetic phenomenon, that seems to be involved in a number of cellular responses. However, so far there is only little information whether DNA methylation is also a component of the mechanisms that lie behind retinal degenerations, such as Retinitis Pigmentosa. Here we wanted to see whether there were any indications of altered DNA methylation in the degenerating photoreceptors that characterize this disease and therefore investigated several animal models for Retinitis Pigmentosa.

Methods: : Retinas were collected from either rd1, rd2 or wild type background C3H mice, as well as from either P23H-1 and S334ter-3 rhodopsin mutant rats or wild type background CD rats at relevant age (postnatal day 11, 21, 20, 12 respectively for rd1, rd2, P23H-1, S334ter-3). The specimens were fixed, cryo-sectioned and immunolabeled for 5-methyl cytosine, either alone or in combination with TUNEL staining for dying cells.

Results: : Methylated DNA was only very rarely found in the photoreceptor layers of wild type retina either from mouse or rat. By contrast, the outer nuclear layers in all of the four models showed distinct staining in a subset of photoreceptors, that corresponded to the expected number of degenerating cells of the respective age. Furthermore, colabelling in rd1 retina showed that the staining for methylated DNA overlapped with TUNEL positive cells to a major extent.

Conclusions: : DNA hypermethylation was detected in degenerating photoreceptors regardless of the different kinds of mutations in the various models, and with characteristics that strongly suggested a relation with the cell death mechanism. These findings are therefore compatible with increased DNA methylation as an important and maybe also a general step in the cell death processes that occur in photoreceptors burdened with inherited degeneration.

Keywords: retinal degenerations: cell biology • photoreceptors • apoptosis/cell death 
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