June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
A peptide derived from Prominin-1 enhances axon regeneration of retinal ganglion cells in an optic nerve injury model
Author Affiliations & Notes
  • Zai-Long Chi
    Department of Ophthalmology, Harvard Medical School, Boston, MA
    Vascular Biology Program, Boston Children's Hospital, Boston, MA
  • Amy E. Birsner
    Department of Ophthalmology, Harvard Medical School, Boston, MA
    Vascular Biology Program, Boston Children's Hospital, Boston, MA
  • Avner Adini
    Department of Ophthalmology, Harvard Medical School, Boston, MA
    Vascular Biology Program, Boston Children's Hospital, Boston, MA
  • Robert D'Amato
    Department of Ophthalmology, Harvard Medical School, Boston, MA
    Vascular Biology Program, Boston Children's Hospital, Boston, MA
  • Footnotes
    Commercial Relationships Zai-Long Chi, None; Amy E. Birsner, None; Avner Adini, None; Robert D'Amato, Boston Childrens Hospital (P)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 417. doi:
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      Zai-Long Chi, Amy E. Birsner, Avner Adini, Robert D'Amato; A peptide derived from Prominin-1 enhances axon regeneration of retinal ganglion cells in an optic nerve injury model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):417.

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

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Abstract

Purpose: Prominin-1 (CD133) is a 5-transmembrane glycoprotein found in both humans and rodents. Prominin-1 was originally identified as a stem cell marker and has been recently identified in neuronal and glial stem cells. It also acts as a key regulator of disk morphogenesis during early retinal development, and mutations in this gene result in retinal degeneration. We recently reported that Prominin-1 interacts with VEGF and enhances its activity. We have developed a short peptide derived from Prominin-1, named PR1P, which also enhances VEGF activity and we investigated its effect on cell death and regeneration of damaged retinal ganglion cells in an optic nerve injury model.

Methods: Primary rat cortical neuron cells and optic nerves obtained from Fischer rats following an optic nerve (ON) crush were utilized in this experiment. Pellets approximately 1 X 1 X 0.6 mm containing either PR1P or vehicle in hydron polymer were cast and implanted into the retrobulbar space at the time of crush. Immunostaining of the retina and optic nerve was performed 2 weeks after surgery and P1P treatment. Total mRNA and proteins were extracted from the retina and optic nerve followed by analysis utilizing PCR arrays, real-time PCR, western blotting and enzyme-linked immunosorbent assay (ELISA) for searching affected genes and proteins by PR1P.

Results: PR1P increased neuronal sprouting in vitro. In vivo, PR1P significantly increased axonal regeneration and prevented retinal ganglion cell (RGC) death. We also observed that PR1P regulated matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) expression resulting in an increased MMP-9/TIMP-1 ratio in both the retina and ON. Additionally, the expression of chemokines such as CCL2/MCP-1 and CXCL2/MIP2-alpha are notably increased after treatment of P1P compared to the control group.

Conclusions: PR1P has neuroprotective activity in the optic nerve crush model. Further development of PR1P as a neuroprotective therapeutic agent is ongoing.

Keywords: 629 optic nerve • 531 ganglion cells • 687 regeneration  
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