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J. Lin, J. Choi, J. Boccio, X. Wang, S. Strittmatter, J. C. Tsai; The Anti-NgR Blocking Protein, NgR(310)ecto-Fc, Has a Potential Role for Neuroprotection in an EVC Rat Model of Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4051.
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The Nogo receptor (NgR) complex provides greater understanding of the mechanisms underlying inhibition of axonal regeneration in the central nervous system. A novel soluble blocking protein, NgR(310)ecto-Fc, binds to ligands (i.e. Nogo, MAG, and OMgp), and has been shown to enhance neuroregeneration in motor neurons after spinal cord injury in animal models.In this pilot study, we sought to determine whether the NgR(310)ecto-Fc protein also promotes the survival and growth of a sensory neuron, such as the retinal ganglion cell (RGC). Our initial findings showed that Nogo is highly expressed in the nerve fiber layer (NFL), Müller cells, and optic nerve tissues. The NgR is mainly expressed in the inner plexiform layer (IPL), but is not detectable in optic nerve tissues.
We investigated the potential neuroprotective and neuroregenerative effects of NgR(310)ecto-Fc in an episcleral vein cauterization (EVC) rat model of glaucoma. The intraocular pressure (IOP) of the treated right eye was elevated to approximately 25 mmHg by EVC. Two dosages of NgR(310)ecto-Fc intravitreal injection (Low: 0.2 ug, and High: 5 ug, both n=6) as well as two control groups (saline vehicle, and 5 ug rat IgG injection, both n=6) were employed in a double- masked, randomized animal study. The treatments were performed at day 0 and day 7. Seven weeks post-injection, we analyzed RGC loss and morphologic changes by FluoroGold retrograde labeling and immunohistology staining.
Significant RGC loss was observed in both control groups compared to the non-treated left eyes. RGC loss was found in both NgR(310)ecto-Fc treatment groups, but slightly less than control groups. Immunohistology staining demonstrated thinner RGC layers in both the control groups and NgR(310)ecto-Fc treated groups compared to non-treated left eyes.
Our primary results suggest that NgR(310)ecto-Fc demonstrates significant neuroprotection effects in an EVC rat model of glaucoma.
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