Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Sep;4(3):104-10.
doi: 10.1007/s12177-012-9079-9. Epub 2012 Mar 20.

A role for epigenetic changes in the development of retinal neurodegenerative conditions

Heather R Pelzel  1 , Robert W Nickells
Affiliations

A role for epigenetic changes in the development of retinal neurodegenerative conditions

Heather R Pelzel et al. J Ocul Biol Dis Infor. 2011 Sep.
No abstract available

Keywords: Acetylation; Epigenetic change; Histones; Neuronal degeneration; Retinal ganglion cell.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Gene expression changes in RGCs associated with deacetylation of histones. a RNase protection assay for transcripts of the RGC-specific gene Thy1. Shortly after optic nerve crush in mice, Thy1 levels are rapidly depleted (left panel). This precedes the loss of RGCs, which begin to drop out of the retina at 1 week after optic nerve damage. The loss of Thy1 also occurs in Bax-deficient mice, which have RGCs completely resistant to the optic nerve crush protocol (right panel, 1 week after ONC). b ChIP assays showing the relative acetylation of promoter histones in genes that decrease in expression after ONC (gray bars) and genes that exhibit an increase in expression (black bars) at 3 days postcrush. Promoter histone deacetylation is correlated with genes that are silenced. c Blocking the activity of class I and II HDACs with TSA prevents the silencing of the Fem1cR3 RGC reporter gene in mice after ONC. In this experiment, TSA was administered to mice 1 day prior to nerve damage, and expression of Fem1c (as a function of β-galactosidase activity) was examined 5 days after surgery. a was reprinted from [29] with permission. b and c were reprinted from [21], which is an open access journal
Fig. 2
Fig. 2
Histone deacetylation and nuclear changes in RGCs after ONC. Immunofluorescent labeling of acetylated histone H4 (AcH4) in the ganglion cell layer of a control mouse eye (a) and an eye 5 days after optic nerve crush (b). Nuclei have been counterstained with DAPI. Eyes with crush exhibit nuclei with reduced or absent staining for AcH4. Nuclear morphology often demonstrates highly condensed chromatin (arrow in b). Scale bar = 10 μm. c Quantification of histone H4 acetylation in the ganglion cell layer of mouse eyes after ONC. Data from this experiment were collected by measuring the pixel density of AcH4 label per total area of each nucleus examined and normalizing this value to the pixel density of unaffected nuclei in the inner nuclear layer. The data are depicted as the ratio of experimental (OS) and control (OD) retinas after ONC. *P ≤ 0.0001 and **P = 0.041 (OS vs. OD at given time point). Transmission electron micrographs of control (d) and experimental (e) mouse retinas. Images were taken in the ganglion cell layer of eyes 5 days after ONC. Control eyes d exhibit round or oval nuclei with lightly staining euchromatin and prominent nucleoli (nu). In crush eyes, nuclei predominantly appear highly convoluted and exhibit the formation of varying degrees of heterochromatin (hc), typically forming along the inner side of the nuclear envelope. Scale bar = 500 nm. c was reprinted from [21], which is an open access journal
Fig. 3
Fig. 3
Changes in HDAC activity in mouse nuclei after ONC. a Total nuclear HDAC activity in control (OD) and experimental (OS) retinas after ONC. Crush retinas exhibit a slow progressive increase in nuclear HDAC activity relative to unaffected eyes. All activity can be inhibited by the broad002Dspectrum inhibitor TSA. b HDAC2 and HDAC3 localization after ONC. HDAC2 is predominantly present in the nuclear fraction of both control and crush retinas. HDAC3, however, redistributes to the nuclear fraction in crush eyes, consistent with the increase in nuclear HDAC activity after crush. Reprinted from [21], which is an open access journal
See this image and copyright information in PMC

References

    1. Yeo S, et al. Characterization of DNA methylation change in stem cell marker genes during differentiation of human embryonic stem cells. Biochem Biophys Res Commun. 2007;359(3):536–42. doi: 10.1016/j.bbrc.2007.05.120. - DOI - PubMed
    1. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21. doi: 10.1101/gad.947102. - DOI - PubMed
    1. Vaquero A, Loyola A, Reinberg D. The constantly changing face of chromatin. Sci Aging Knowledge Environ. 2003;2003(14):RE4. doi: 10.1126/sageke.2003.14.re4. - DOI - PubMed
    1. Happel N, Doenecke D. Histone H1 and its isoforms: contribution to chromatin structure and function. Gene. 2009;431(1–2):1–12. doi: 10.1016/j.gene.2008.11.003. - DOI - PubMed
    1. Cosgrove MS, Boeke JD, Wolberger C. Regulated nucleosome mobility and the histone code. Nat Struct Mol Biol. 2004;11(11):1037–43. doi: 10.1038/nsmb851. - DOI - PubMed

LinkOut - more resources