IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms9005.html
   My bibliography  Save this article

A short N-terminal domain of HDAC4 preserves photoreceptors and restores visual function in retinitis pigmentosa

Author

Listed:
  • Xinzheng Guo

    (Yale University School of Medicine)

  • Shao-Bin Wang

    (Yale University School of Medicine)

  • Hongping Xu

    (Yale University School of Medicine)

  • Adema Ribic

    (Tufts University School of Medicine)

  • Ethan J. Mohns

    (Yale University School of Medicine)

  • Yu Zhou

    (Sichuan Provincial Key Laboratory for Human Disease Gene Study and Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital
    Hospital of University of Electronic Science and Technology of China (UESTC) & Sichuan Provincial People's Hospital)

  • Xianjun Zhu

    (Sichuan Provincial Key Laboratory for Human Disease Gene Study and Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital
    Hospital of University of Electronic Science and Technology of China (UESTC) & Sichuan Provincial People's Hospital)

  • Thomas Biederer

    (Tufts University School of Medicine)

  • Michael C. Crair

    (Yale University School of Medicine)

  • Bo Chen

    (Yale University School of Medicine
    Yale University School of Medicine)

Abstract

Retinitis pigmentosa is a leading cause of inherited blindness, with no effective treatment currently available. Mutations primarily in genes expressed in rod photoreceptors lead to early rod death, followed by a slower phase of cone photoreceptor death. Rd1 mice provide an invaluable animal model to evaluate therapies for the disease. We previously reported that overexpression of histone deacetylase 4 (HDAC4) prolongs rod survival in rd1 mice. Here we report a key role of a short N-terminal domain of HDAC4 in photoreceptor protection. Expression of this domain suppresses multiple cell death pathways in photoreceptor degeneration, and preserves even more rd1 rods than the full-length HDAC4 protein. Expression of a short N-terminal domain of HDAC4 as a transgene in mice carrying the rd1 mutation also prolongs the survival of cone photoreceptors, and partially restores visual function. Our results may facilitate the design of a small protein therapy for some forms of retinitis pigmentosa.

Suggested Citation

  • Xinzheng Guo & Shao-Bin Wang & Hongping Xu & Adema Ribic & Ethan J. Mohns & Yu Zhou & Xianjun Zhu & Thomas Biederer & Michael C. Crair & Bo Chen, 2015. "A short N-terminal domain of HDAC4 preserves photoreceptors and restores visual function in retinitis pigmentosa," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9005
    DOI: 10.1038/ncomms9005
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms9005
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms9005?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9005. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.