Abstract
Purpose :
Age-related macular degeneration (ARMD), a progressive retinal degenerative disorder, is the 3rd cause of blindness worldwide but few treatments exist to halt progression. Riluzole is an FDA-approved drug of the benzothiazole class previously shown to have neuroprotective effects in an experimental glaucoma model. We tested the hypothesis that riluzole would protect against retinal degeneration in an experimental mouse model of light-induced retinal injury.
Methods :
BALB/c albino mice (male or female; 6 weeks old) were divided into 2 groups: control-treated mice and riluzole-treated mice. Light injury mice were exposed to 6,000 lux-cool, white, fluorescent light for 2 hours to induce light injury. Control (1.6% DMSO in normal saline) or riluzole (8 mg/kg/day freshly prepared in normal saline before injection; stock solution at 20mg/mL in DMSO) was injected intraperitoneally after light injury for 6 days. Scotopic electroretinography (ERG) was recorded before and 1 week after light injury. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed 48 hours after light injury.
Results :
Before retinal light injury, average ERG a- and b-wave amplitudes were 448±44 μV and 856±91 μV, respectively, in the control group and 448±37 μV and 869±80 μV, respectively, in the riluzole-treated group at log 2.1 cd s/m2 light intensity. Following retinal light injury, a-wave amplitudes were 112±27 μV in the control group and 268±51 μV in the riluzole-treated group (p<0.01); b-wave amplitudes were 240±68 μV in the control group and 544±107 μV in the riluzole-treated group at log 2.1 cd s/m2 light intensity (p<0.03). Riluzole treatments significantly attenuated light injury-induced retinal functional impairment as compared to control-treated mice. Furthermore, retinal light injury produced significant outer nuclear layer cell TUNEL-positive signals, while outer nuclear layer TUNEL positive cells were significantly less with riluzole treatment 48 hours after light injury.
Conclusions :
Riluzole treatment demonstrated a substantial effect on preserving ERG a- and b-wave amplitudes following retinal light injury as compared to the control group. Riluzole treatment also decreased outer nuclear layer TUNEL positive cells, suggesting that riluzole may play a role in inhibiting retinal photoreceptor degeneration. These initial findings suggest that riluzole may become a novel therapeutic agent for ARMD.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.