Calcium antagonists in N-methyl d-aspartate-induced retinal injury

Graefes Arch Clin Exp Ophthalmol. 2003 May;241(5):418-22. doi: 10.1007/s00417-002-0610-8. Epub 2003 Apr 16.

Abstract

Purpose: To detect the neuroprotective role of nimodipine and dantrolene in N-methyl- d-aspartate (NMDA)-induced retinal injury.

Methods: In this study we used two calcium antagonists which have two different modes of action, nimodipine and dantrolene, to prevent NMDA-induced retinal ischemia in guinea pigs. In 40 animals we injected nimodipine (n=10), dantrolene (n=10), a combination of both (n=10) or sterile 0.9% NaCl solution as a placebo (n=10) before intravitreal injection of NMDA. We enucleated one eye of each animal after 48 hours and performed histopathologic examination. We also measured malondialdehyde (MDA) levels in retinal homogenates as a marker of ischemic injury.

Results: Our results indicate that ganglion cells of the retina were preserved mostly by nimodipine, followed by combined nimodipine-dantrolene, and dantrolene respectively. The ganglion cell count was statistically significantly higher in cases where we used calcium antagonists than in the control group (p<0.05). We also found that MDA was significantly reduced by calcium antagonists compared to the control group (p<0.05).

Conclusion: Our data show that nimodipine and dantrolene both have potential neuroprotective effects; nimodipine preserved retinal ganglion cells to a greater extent than dantrolene from NMDA-induced retinal injury.

MeSH terms

  • Animals
  • Calcium Channel Blockers / therapeutic use*
  • Cell Count
  • Dantrolene / therapeutic use
  • Drug Therapy, Combination
  • Excitatory Amino Acid Agonists / toxicity*
  • Guinea Pigs
  • Ischemia / chemically induced
  • Ischemia / metabolism
  • Ischemia / pathology
  • Ischemia / prevention & control*
  • Male
  • Malondialdehyde / metabolism
  • N-Methylaspartate / toxicity*
  • Nimodipine / therapeutic use
  • Retina / drug effects
  • Retinal Diseases / chemically induced
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology
  • Retinal Diseases / prevention & control*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Retinal Vessels / drug effects*
  • Retinal Vessels / metabolism

Substances

  • Calcium Channel Blockers
  • Excitatory Amino Acid Agonists
  • Malondialdehyde
  • Nimodipine
  • N-Methylaspartate
  • Dantrolene