Limited restoration of visual function after partial optic nerve injury; a time course study using the calcium

Marion Selt1, Carole A Bartlett, Alan R Harvey

  • 1Experimental and Regenerative Neurosciences, The University of Western Australia, Crawley, 6009 WA, Australia.

Brain Research Bulletin
|November 17, 2009
PubMed

Insights

One month of lomerizine dihydrochloride treatment is necessary to protect retinal ganglion cells and restore visual function after optic nerve injury. Shorter treatments or cessation of lomerizine dihydrochloride lead to loss of benefits.

Area of Science:

  • Neuroscience
  • Ophthalmology
  • Pharmacology

Background:

  • Secondary degeneration, characterized by neuronal and glial damage due to increased calcium influx, occurs adjacent to primary injuries.
  • Lomerizine dihydrochloride, a calcium channel blocker with central nervous system effects, is being investigated for glaucoma treatment.
  • Previous studies showed lomerizine dihydrochloride protects retinal ganglion cells (RGCs) and limits macrophage infiltration after optic nerve injury.

Purpose of the Study:

  • To determine if shorter treatment durations (1 day or 1 week) of lomerizine dihydrochloride improve RGC survival and visual function.
  • To assess if the benefits of lomerizine dihydrochloride treatment are sustained after its cessation.
  • To establish the minimum effective treatment period for lomerizine dihydrochloride in optic nerve injury models.

Main Methods:

  • Partial transection of the optic nerve in a preclinical model.
  • Administration of lomerizine dihydrochloride for varying durations (1 day, 1 week, 1 month).
  • Assessment of RGC survival, visual function (optokinetic nystagmus), and macrophage infiltration.

Main Results:

  • One month of lomerizine dihydrochloride treatment was the minimum duration required to restore and maintain the fast reset phase of optokinetic nystagmus for 2 months post-treatment.
  • One week of lomerizine dihydrochloride treatment provided only temporary recovery of fast reset phases, which were not sustained after treatment cessation.
  • Sustained RGC density protection required 1 month of lomerizine dihydrochloride treatment, but this protection was not maintained after treatment cessation.
  • No lomerizine dihydrochloride treatment protocol fully restored visual function.

Conclusions:

  • A minimum of 1 month of lomerizine dihydrochloride treatment is essential for sustained RGC protection and visual function recovery following optic nerve injury.
  • Shorter treatment durations or discontinuation of lomerizine dihydrochloride limits long-term therapeutic benefits.
  • Combining lomerizine dihydrochloride with other therapeutic strategies is necessary for complete visual function restoration.

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