Riluzole- and Resveratrol-Induced Delay of Retinal Ganglion Cell Death in an Experimental Model of Glaucoma

Curr Eye Res. 2016;41(1):59-69. doi: 10.3109/02713683.2015.1004719. Epub 2015 Feb 6.

Abstract

Purpose: To evaluate the effects of the neuroprotective agents riluzole and resveratrol on the survival of retinal ganglion cells (RGCs) when administered alone or in combination.

Materials and methods: Experimental glaucoma was induced by injecting hyaluronic acid into the anterior chamber of Wistar albino rats weekly for a six-week period. Intraocular pressure was measured before and immediately after glaucoma induction. The neuroprotective effects of daily intraperitoneal injections of riluzole (8 mg/kg) and resveratrol (10 mg/kg) were evaluated and compared. After the six-week period, dextran tetramethylrhodamine was applied into the optic nerve and the density of surviving RGCs was evaluated by counting the labeled RGCs in whole mount retinas for retrograde labeling of RGCs.

Results: The mean numbers of RGCs were significantly preserved in all treatment groups compared to the vehicle-treated glaucoma group (G). The mean number of RGCs in mm(2) were 1207 ± 56 in the control group (C), 404 ± 65 in G group, 965 ± 56 in riluzole-treated group in the early phase of glaucoma (E-Ri), 714 ± 25 in riluzole-treated group in the late phase of glaucoma (L-Ri), 735 ± 29 in resveratrol-treated group in the early phase of glaucoma (E-Re), 667 ± 20 in resveratrol-treated group in the late phase of glaucoma (L-Re), and 1071 ± 49 in riluzole and resveratrol combined-treated group in the early phase of glaucoma (E-RiRe group).

Conclusions: When used either alone or in combination, both riluzole and resveratrol, two agents with different mechanisms of action in glaucoma, significantly delayed RGC loss in this study's experimental glaucoma model.

Keywords: Glaucoma; neuroprotection; resveratrol; retinal ganglion cell; riluzole.

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Cell Count
  • Cell Survival / drug effects
  • Disease Models, Animal*
  • Drug Therapy, Combination
  • Glaucoma / drug therapy*
  • Glaucoma / physiopathology
  • Injections, Intraperitoneal
  • Intraocular Pressure / drug effects
  • Male
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Wistar
  • Resveratrol
  • Retinal Ganglion Cells / drug effects*
  • Retinal Ganglion Cells / pathology
  • Riluzole / therapeutic use*
  • Stilbenes / therapeutic use*
  • Tonometry, Ocular

Substances

  • Antioxidants
  • Neuroprotective Agents
  • Stilbenes
  • Riluzole
  • Resveratrol