June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Role Of Neuritin 1 in Response to Optic Nerve Crush
Author Affiliations & Notes
  • Tasneem Putliwala
    CBAN - Visual Sciences, UNTHSC, Fort Worth, TX
    NTERI, UNTHSC, Fort Worth, TX
  • Yang Liu
    CBAN - Visual Sciences, UNTHSC, Fort Worth, TX
    NTERI, UNTHSC, Fort Worth, TX
  • Robert Wordinger
    CBAN - Visual Sciences, UNTHSC, Fort Worth, TX
    NTERI, UNTHSC, Fort Worth, TX
  • Abbot Clark
    CBAN - Visual Sciences, UNTHSC, Fort Worth, TX
    NTERI, UNTHSC, Fort Worth, TX
  • Footnotes
    Commercial Relationships Tasneem Putliwala, None; Yang Liu, None; Robert Wordinger, None; Abbot Clark, Alcon Research, Ltd. (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 431. doi:https://doi.org/
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    • Get Citation

      Tasneem Putliwala, Yang Liu, Robert Wordinger, Abbot Clark; Role Of Neuritin 1 in Response to Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2013;54(15):431. doi: https://doi.org/.

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

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Abstract

Purpose: Glaucoma is a progressive optic neuropathy characterized by axonal injury, retinal ganglion cell (RGC) loss, and visual field defects. Neuritin1 (Nrn1) is an extracellular, GPI-linked protein, which can be secreted as a soluble form. It stimulates axonal plasticity, dendritic arborization, and synapse maturation in the CNS. The purpose of this study was to evaluate the expression of Nrn1 using an in vivo optic nerve crush (ONC) mouse model that mimics features of glaucoma axonopathy.

Methods: Unilateral ONC was performed on 8-10-week-old BALB/cJ eyes using the Nickell’s technique. Retinas (N=8) and ONs (N=6) were harvested at six different time points (0, 3, 7, 14, 21, and 28 days) post crush (dpc). Real time PCR and immunohistochemistry (IHC) was performed to evaluate spatial and temporal Nrn1 expression in the retina and ON.

Results: After ONC, Nrn1 gene expression in the retina was significantly decreased progressively by 7 dpc from control (p<0.05), with a slight recovery by 14 dpc and then a significant reduction by 21 dpc (p<0.001). In contrast, we observed basal expression till 21 dpc in the ON, with a significant increase at 28 dpc (p<0.05). Corresponding, biphasic NRN1 expression patterns were observed in both retina and ON IHC sections.

Conclusions: Degeneration of neurons and axonopathy are classical hallmarks of glaucoma neuropathy, which is evident in other neurodegenerative diseases such as Parkinson and Alzheimer’s. Nrn1, a vital player in neuronal plasticity, exhibited a biphasic recovery pattern after ONC suggesting that modifications in the regenerative ability of the neurons leads to RGC and ON axonal injury. Future studies will determine whether Nrn1 gene therapy can prevent the loss of neurons by reviving regeneration of RGCs after optic nerve axonopathy.

Keywords: 531 ganglion cells • 629 optic nerve • 533 gene/expression  
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