Cannabinoid-mediated retinal rescue correlates with improved circadian parameters in retinal dystrophic rats

Abstract

Ocular pathologies and blindness have been linked to circadian disorders. In previous studies, our group has demonstrated that retinitis pigmentosa is associated with degenerative changes in the melanopsin system and weaker circadian patterns. We have also shown that cannabinoids preserve retinal structure and function in dystrophic P23H rats. This study is consequently aimed at examining whether the morphologic and functional rescue of retinal degeneration by cannabinoids is associated with amelioration of circadian parameters. The synthetic cannabinoid HU210 (100 μg/kg, i.p.) or vehicle were administered to transgenic P23H rats three times per week, from postnatal day 24-90. Sprague-Dawley rats were used as a healthy control group. Locomotor activity and scotopic electroretinograms were recorded, and the retinal structure was analyzed at the end of the experiment. The ERG a- and b-wave amplitudes and photoreceptor cell number were more deteriorated in vehicle-administered P23H rats as compared to P23H rats treated with HU210. In cannabinoid-administered P23H rats, the locomotor activity circadian rhythms showed less disturbance than that observed in vehicle-administered P23H rats, the latter showing lower values for mesor, amplitude, acrophase, percentage of variance and non-parametric variables. A positive linear correlation was found between retinal values and circadian parameters of locomotor activity from P23H rats. This study thus provides evidence of a positive correlation between cannabinoid-mediated rescue of retinal structure and function and improvement of circadian rhythmicity.

Keywords: Circadian rhythms; HU210; P23H; Retinal degeneration; Retinitis pigmentosa.