Deimination restores inner retinal visual function in murine demyelinating disease

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)646-656
Number of pages11
JournalJournal of Clinical Investigation
Volume123
Issue number2
DOIs
StatePublished - Feb 1 2013

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Demyelinating Diseases
Multiple Sclerosis
Neurites
Neurons
Retinal Ganglion Cells
Protein Biosynthesis
Carisoprodol
Post Translational Protein Processing
Dendrites
Small Interfering RNA
Transgenic Mice
Axons
Carrier Proteins
Proteins
Down-Regulation

ASJC Scopus subject areas

  • Medicine(all)

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Deimination restores inner retinal visual function in murine demyelinating disease. / Enriquez-Algeciras, Mabel; Ding, Di; Mastronardi, Fabrizio G.; Marc, Robert E.; Porciatti, Vittorio; Bhattacharya, Sanjoy K.

In: Journal of Clinical Investigation, Vol. 123, No. 2, 01.02.2013, p. 646-656.

Research output: Contribution to journalArticle

Enriquez-Algeciras, Mabel ; Ding, Di ; Mastronardi, Fabrizio G. ; Marc, Robert E. ; Porciatti, Vittorio ; Bhattacharya, Sanjoy K. / Deimination restores inner retinal visual function in murine demyelinating disease. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 2. pp. 646-656.
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