TY - JOUR

T1 - The inhibition of the degrading enzyme fatty acid amide hydrolase alters the activity of the cone system in the vervet monkey retina

AU - Bouskila, Joseph

AU - Bleau, Maxime

AU - Micaelo-Fernandes, Catarina

AU - Bouchard, Jean François

AU - Ptito, Maurice

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - Recent studies using full-field electroretinography (ffERG) that triggers a non-specific mass response generated by several retinal sources have attributed an important role for cannabi-noid receptors in mediating vision in primates. Specific cone-mediated responses evoked through the photopic flicker ERG appear to be a better way to validate the assumption that endogenous cannabinoids modulate the cone pathway, since FAAH is mainly expressed in the vervet monkey cone photoreceptors. The aim of this study is two-fold: (1) to use the photopic flicker ERG to target the cone pathway specifically, and (2) use URB597 as a selective inhibitor of the endocannabinoid degrading enzyme Fatty Acid Amide Hydrolase (FAAH) to enhance the levels of fatty acid amides, particularly anandamide. We recorded ERGs under four different flicker frequencies (15, 20, 25, and 30 Hz) in light-adapted conditions after intravitreal injections of URB597. Our results show that intravitreal injections of URB597, compared to the vehicle DMSO, increased significantly ffERG amplitudes at 30 Hz, a frequency that solely recruits cone activity. However, at 15 Hz, a frequency that activates both rods and cones, no significant difference was found in the ERG response amplitude. Additionally, we found no differences in implicit times after URB597 injections compared to DMSO vehicle. These results support the role of molecules degraded by FAAH in cone-mediated vision in non-human primates.

AB - Recent studies using full-field electroretinography (ffERG) that triggers a non-specific mass response generated by several retinal sources have attributed an important role for cannabi-noid receptors in mediating vision in primates. Specific cone-mediated responses evoked through the photopic flicker ERG appear to be a better way to validate the assumption that endogenous cannabinoids modulate the cone pathway, since FAAH is mainly expressed in the vervet monkey cone photoreceptors. The aim of this study is two-fold: (1) to use the photopic flicker ERG to target the cone pathway specifically, and (2) use URB597 as a selective inhibitor of the endocannabinoid degrading enzyme Fatty Acid Amide Hydrolase (FAAH) to enhance the levels of fatty acid amides, particularly anandamide. We recorded ERGs under four different flicker frequencies (15, 20, 25, and 30 Hz) in light-adapted conditions after intravitreal injections of URB597. Our results show that intravitreal injections of URB597, compared to the vehicle DMSO, increased significantly ffERG amplitudes at 30 Hz, a frequency that solely recruits cone activity. However, at 15 Hz, a frequency that activates both rods and cones, no significant difference was found in the ERG response amplitude. Additionally, we found no differences in implicit times after URB597 injections compared to DMSO vehicle. These results support the role of molecules degraded by FAAH in cone-mediated vision in non-human primates.

KW - Cone pathway

KW - Endocannabinoids

KW - FAAH

KW - Flicker electroretinogram

KW - Retina

KW - URB597

KW - Vervet monkeys

U2 - 10.3390/brainsci11111418

DO - 10.3390/brainsci11111418

M3 - Journal article

C2 - 34827417

AN - SCOPUS:85118237540

VL - 11

JO - Brain Sciences

JF - Brain Sciences

SN - 2076-3425

IS - 11

M1 - 1418

ER -