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Partial Optic Nerve Transection in Rats: A Model Established with a New Operative Approach to Assess Secondary Degeneration of Retinal Ganglion Cells
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Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve

Lillian M Toomey1, Carole A Bartlett1, Maimuna Majimbi2

  • 1Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, 35 Stirling Hwy, Perth, WA, 6009, Australia.

Experimental Brain Research
|October 28, 2018
PubMed

Insights

A new drug combination, lomerizine plus Brilliant Blue G (BBG) and YM872, effectively limits secondary degeneration after optic nerve injury. This treatment preserves nerve structure and visual function, offering a promising alternative for neurotrauma recovery.

Area of Science:

  • Neuroscience
  • Ophthalmology
  • Pharmacology

Background:

  • Secondary degeneration following neurotrauma exacerbates neuronal and glial loss, leading to functional deficits.
  • Previous studies indicated that a combination of ion channel inhibitors (lomerizine + oxATP + YM872) could mitigate secondary degeneration.
  • Brilliant Blue G (BBG) is a more clinically applicable P2X7 receptor inhibitor than oxATP.

Purpose of the Study:

  • To evaluate the efficacy of a novel ion channel inhibitor combination (lomerizine + BBG + YM872) in limiting secondary degeneration after optic nerve injury.
  • To compare the effectiveness of BBG-containing combination with the oxATP-containing combination in a rat model.

Main Methods:

  • Partial optic nerve transection was performed in adult female rats to induce secondary degeneration.
  • Animals received local treatment via osmotic mini-pump with either lomerizine + oxATP + YM872 or lomerizine + BBG + YM872.
  • Evaluated outcomes included microglial/macrophage counts (Iba1+, ED1+), oligodendroglial cell numbers, node/paranode structure, and visual function (optokinetic nystagmus test).

Main Results:

  • The lomerizine + BBG + YM872 combination demonstrated comparable efficacy to the lomerizine + oxATP + YM872 combination in preserving node/paranode structure and visual function.
  • Neither combination significantly improved microglial/macrophage or oligodendroglial cell counts compared to vehicle controls.
  • Local delivery of the BBG-based ion channel inhibitor combination effectively limited secondary degeneration.

Conclusions:

  • A locally delivered combination of lomerizine, BBG, and YM872 is as effective as the oxATP-containing combination in limiting secondary degeneration after partial optic nerve injury.
  • This BBG-based combination shows promise for preserving structural integrity and visual function in neurotrauma models.
  • Further research may be needed to enhance effects on glial cell populations.
Keywords:
Ion channel inhibitorMyelinNeurotraumaSecondary degenerationVisual function

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