Abstract
Purpose :
Retinal diseases that damage photoreceptors, particularly those that affect cones such as the “dry” form of age-related macular degeneration (AMD), have dire consequences for vision. Models of light-induced retinal degeneration (LIRD) recapitulate some of the hallmarks of oxidative damage observed in “dry” AMD. One strategy for treatment of AMD, is to employ a “druggable” therapy targeted to neuroprotective mechanisms in photoreceptors. Cannabinoids have been shown to prevent oxidative stress-driven damage in central neurons, thus preventing neurodegeneration. The purpose of this study was to test whether targeting cannabinoid receptors could prevent light damage to photoreceptors in zebrafish retina.
Methods :
Adult Tg(nrd:GFP) zebrafish (used to GFP label rod photoreceptors) were dark-adapted for 24 hrs, followed by intravitreal injections of a mixed cannabinoid receptor agonist, 1 µM CB13 (CB1/CB2). Controls were injected with saline in both eyes. All zebrafish were exposed to high-intensity light (≥ 28,000 lux) and collected at 0 and 96 hours post dark-adaptation. Immunohistochemical analysis was performed with cell specific markers, and cell death assays on zebrafish retinas in order to assess the impact of CB13 on light-induced photoreceptor damage of rods and cones.
Results :
Photoreceptors treated with 96 hours of light exposure exhibited severe truncation or loss of the outer segments and swelling. Additionally, there was an increase in cell death and a significant decrease in rod and cone photoreceptors. Treatment of retinas with 1 µM CB-13 prior to light lesioning prevented cell damage, and reduced truncation of the outer segments, lacked swelling, and had morphology similar to retinas collected prior to light exposure.
Conclusions :
These findings demonstrate that cannabinoids have the capacity to prevent oxidative stress-driven light damage following intense light exposure. Thus, cannabinoids could serve as a potential novel therapeutic target for the treatment of the dry form of AMD.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.