May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Role of Histone Acetylation/Deacetylation on Early Changes in Gene Expression in Retinal Ganglion Cells Following Optic Nerve Crush
Author Affiliations & Notes
  • H. R. Pelzel
    Ophthalmology and Visual Sciences, University of Wisconsin - Madison, Madison, Wisconsin
  • C. L. Schlamp
    Ophthalmology and Visual Sciences, University of Wisconsin - Madison, Madison, Wisconsin
  • R. W. Nickells
    Ophthalmology and Visual Sciences, University of Wisconsin - Madison, Madison, Wisconsin
  • Footnotes
    Commercial Relationships  H.R. Pelzel, None; C.L. Schlamp, None; R.W. Nickells, None.
  • Footnotes
    Support  R01 EY12223, NIH Grant EY016665, Research to Prevent Blindness Grant
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4953. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      H. R. Pelzel, C. L. Schlamp, R. W. Nickells; The Role of Histone Acetylation/Deacetylation on Early Changes in Gene Expression in Retinal Ganglion Cells Following Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4953. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : The loss of retinal ganglion cells during glaucoma occurs by apoptosis. Both decreases and increases in gene expression are early events in the apoptotic pathway. We examined what role promoter histone acetylation levels play in these gene expression changes.

Methods: : Histone deacetylase (HDAC) activity assays were performed on nuclear protein extracts from retinas harvested from mice 1, 3, 5, and 7 days after optic nerve crush (ONC). Western blots (WB) and immunofluorescence (IF) were used to determine the presence and localization of HDACs in the mouse retina. Chromatin immunoprecipitations (ChIP) with antibodies against acetylated H4 histones and quantitative mRNA analyses were performed on samples from retinas following ONC to compare patterns in promoter histone acetylation and expression of select genes - Thy1, BclX, Brn3b, Fem1c, Bim, and GFAP.

Results: : HDAC activity assays showed a significant increase in HDAC activity at 5 day (P=0.07) and 7 days (P=0.021) post-ONC. WB analysis showed that HDACs 2 and 3 were the predominant isoforms in the murine retina. Preliminary results from WB and IF experiments demonstrated HDAC 3 localization changed from cytosolic to nuclear following ONC. IF experiments also showed a concomitant decrease in histone H4 acetylation in the ganglion cell layer, but not the inner nuclear layer. ChIP and mRNA analysis revealed a correlation between changes in histone acetylation and transcript levels after ONC. Genes that become down-regulated, such as Thy1, show a decrease in histone acetylation, while genes that become up-regulated, such as Bim, show an increase.

Conclusions: : The data illustrate that early changes in gene expression may be regulated by promoter histone acetylation status. The role of histone acetylation/deacetylation in the ganglion cell apoptotic program is being studied further using inhibitors of HDAC activity.

Keywords: apoptosis/cell death • ganglion cells • gene/expression 
×
×

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.

×