Abstract:

Nervous system emerges from complex signaling interactions where extrinsic (neurotransmitters and trophic factors, among others) and intrinsic factors (transcription factors) interplay in the developing tissue to control gene activity promoting chronic changes in cell genesis, migration, differentiation and death. The retinal microenvironment is regulated by a broad variety of chemicals, including endocannabinoids and nucleotides that modulate embryonic progenitor-neuron-Müller glia signaling in very early developing or pathophysiological conditions. Accumulated evidence demonstrate the presence of a functional cannabinoid system in this tissue, with many retina cell types expressing cannabinoid CB1 and/or CB2 receptors, the two main ligands N-arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG) and enzymes that generate N-acyl phosphatidylethanolamine phospholipase, and diacylglycerol lipase (DAGL) and degrade fatty acid amide hydrolase, monoacylglycerol lipase (MAGL) and cyclooxygenase-2 endocannabinoids. As in other areas of the central nervous system, cannabinoids seem to regulate neurotransmission in the retina by inhibiting the release of transmitters such as dopamine, norepinephrine, γ-aminobutyric acid and glutamate. They also play an important role in retinal circuitry and in scotopic vision by modulating Ca 2+ and K + channels in bipolar cells and photoreceptors. Moreover, under pathological conditions, cannabinoids seem to induce neuroprotection in this tissue. Albeit these protective effects, however, recent data are implicating cannabinoid receptors in cell death in the retina, both in the early developing and diseased tissue.