Cannabinoid Receptor Type 1 Expression in the Developing Avian Retina: Morphological and Functional Correlation With the Dopaminergic System

The avian retina has been used as a model to study signaling by different neuro- and gliotransmitters. It is unclear how dopaminergic and cannabinoid systems are related in the retina. Here we studied the expression of type 1 and 2 cannabinoid receptors (CB(1) and CB(2)), as well as monoacylglycerol lipase (MAGL), the enzyme that degrades 2-arachidonoylglycerol (2-AG), during retina development. Our data show that CB(1) receptor is highly expressed from embryonic day 5 (E5) until post hatched day 7 (PE7), decreasing its levels throughout development. CB(1) is densely found in the ganglion cell layer (GCL) and inner plexiform layer (IPL). CB(2) receptor was also found from E5 until PE7 with a decrease in its contents from E9 afterwards. CB(2) was mainly present in the lamination of the IPL at PE7. MAGL is expressed in all retinal layers, mainly in the IPL and OPL from E9 to PE7 retina. CB(1) and CB(2) were found both in neurons and glia cells, but MAGL was only expressed in Müller glia. Older retinas (PE7) show CB(1) positive cells mainly in the INL and co-expression of CB(1) and tyrosine hydroxylase (TH) are shown in a few cells when both systems are mature. CB(1) co-localized with TH and was heavily associated to D(1) receptor labeling in primary cell cultures. Finally, cyclic AMP (cAMP) was activated by the selective D(1) agonist SKF38393, and inhibited when cultures were treated with WIN55, 212–2 (WIN) in a CB(1) dependent manner. The results suggest a correlation between the endocannabinoid and dopaminergic systems (DSs) during the avian retina development. Activation of CB(1) limits cAMP accumulation via D(1) receptor activation and may influence embryological parameters during avian retina differentiation.