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J. Lin, J.-Y. Choi, S. Viviano, J. Boccio, X.-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. 2010;51(13):3183.
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NgR is implicated in neuronal plasticity and regeneration. Its relative importance in mediating myelin inhibition in vitro and in vivo is currently under investigation, since this protein might be targeted for treatment of various neurological conditions such as spinal cord injury and glaucoma. In this pilot study, we investigated the effects of NgR(310)ecto-Fc protein, a NgR blocking protein, which binds to ligands (i.e. Nogo, MAG, and OMgp), and has been shown to enhance neuroregeneration in motor neurons following spinal cord injury in animal models. We sought to determine whether the NgR(310)ecto-Fc protein also promotes the survival and growth of retinal ganglion cells (RGCs) in an episcleral vein cauterization (EVC) rat model of glaucoma.
We investigated the potential neuroprotective effects of NgR(310)ecto-Fc in an EVC rat model of glaucoma. The intraocular pressure (IOP) of the treated right eye was elevated from baseline 10 mmHg to approximately 25 mmHg by EVC. Three dosages of NgR(310)ecto-Fc intravitreal injection (Low: 0.2 ug, Medium: 1 ug, and High: 5 ug, All N=6) as well as two control groups (PBS vehicle, and 5 ug rat IgG injection, Both N=6) were employed in a double-masked, randomized animal study. Two intravitreal injections were performed at day 0 and day 7. Seven weeks post-injection, we analyzed the extent of RGC loss and morphologic change by FluoroGold retrograde labeling and immunohistology staining. All left eyes were employed as baseline control (no EVC, no treatment).
Significant reductions (P<0.05) in large RGC density were observed in EVC (right) eyes vs non-EVC (left) eyes in all groups. The reduction of large RGC in NgR(310)ecto-Fc in all three treatment groups is significantly (P<0.05) less than in two control groups (Low dosage: ±11% decrease, Medium: ±11%, and High: ±13%) vs (PBS: ±21%, and rat IgG: ±20% ). Immunohistology staining also demonstrated that RGC layer thickness is reduced in all three NgR(310)ecto-Fc treated groups (Low dosage: ±10% decrease, Medium: ±9%, and High: ±10%).
Our preliminary results suggest that NgR(310)ecto-Fc may have neuroprotective effects in an EVC rat model of glaucoma.
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