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 (CB₁ and CB₂), as well as monoacylglycerol lipase (MAGL), the enzyme that degrades 2-arachidonoylglycerol (2-AG), during retina development. Our data show that CB₁ receptor is highly expressed from embryonic day 5 (E5) until post hatched day 7 (PE7), decreasing its levels throughout development. CB₁ is densely found in the ganglion cell layer (GCL) and inner plexiform layer (IPL). CB₂ receptor was also found from E5 until PE7 with a decrease in its contents from E9 afterwards. CB₂ 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. CB₁ and CB₂ were found both in neurons and glia cells, but MAGL was only expressed in Müller glia. Older retinas (PE7) show CB₁positive cells mainly in the INL and co-expression of CB₁ and tyrosine hydroxylase (TH) are shown in a few cells when both systems are mature. CB₁ co-localized with TH and was heavily associated to D₁ receptor labeling in primary cell cultures. Finally, cyclic AMP (cAMP) was activated by the selective D₁ agonist SKF38393, and inhibited when cultures were treated with WIN55, 212-2 (WIN) in a CB₁ dependent manner. The results suggest a correlation between the endocannabinoid and dopaminergic systems (DSs) during the avian retina development. Activation of CB₁ limits cAMP accumulation via D₁ receptor activation and may influence embryological parameters during avian retina differentiation.