Deimination restores inner retinal visual function in murine demyelinating disease
Mabel Enriquez-Algeciras, … , Vittorio Porciatti, Sanjoy K. Bhattacharya
Mabel Enriquez-Algeciras, … , Vittorio Porciatti, Sanjoy K. Bhattacharya
Published February 1, 2013; First published January 2, 2013
Citation Information: J Clin Invest. 2013;123(2):646-656. https://doi.org/10.1172/JCI64811.
View: Text | PDF
Research Article Autoimmunity

Deimination restores inner retinal visual function in murine demyelinating disease

Abstract

Progressive loss of visual function frequently accompanies demyelinating diseases such as multiple sclerosis (MS) and is hypothesized to be the result of damage to the axons and soma of neurons. Here, we show that dendritic impairment is also involved in these diseases. Deimination, a posttranslational modification, was reduced in the retinal ganglion cell layer of MS patients and in a transgenic mouse model of MS (ND4 mice). Reduced deimination accompanied a decrease in inner retinal function in ND4 mice, indicating loss of vision. Local restoration of deimination dramatically improved retinal function and elongation of neurites in isolated neurons. Further, neurite length was decreased by downregulation of deimination or siRNA knockdown of the export-binding protein REF, a primary target for deimination in these cells. REF localized to dendrites and bound selective mRNAs and translation machinery to promote protein synthesis. Thus, protein deimination and dendritic outgrowth play key roles in visual function and may be a general feature of demyelinating diseases.

Authors

Mabel Enriquez-Algeciras, Di Ding, Fabrizio G. Mastronardi, Robert E. Marc, Vittorio Porciatti, Sanjoy K. Bhattacharya

×
Problems with a PDF?

This file is in Adobe Acrobat (PDF) format. If you have not installed and configured the Adobe Acrobat Reader on your system.

Having trouble reading a PDF?

PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.

Having trouble saving a PDF?

Many versions of the free Acrobat Reader do not allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users: Right-click on the Download link and choose the option that says something like "Save Link As...". Mac users should hold the mouse button down on the link to get these same options.

Having trouble printing a PDF?

  1. Try printing one page at a time or to a newer printer.
  2. Try saving the file to disk before printing rather than opening it "on the fly." This requires that you configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can usually be done in the "Helper Applications" options.
  3. Make sure you are using the latest version of Adobe's Acrobat Reader.

Supplemental data - Download (1.54 MB)

Advertisement