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