Cannabidiol (CBD), a non-psychotropic, non-toxic compound has been shown to block diabetes- and endotoxin-induced retinal damage. However, the protective mechanism of this anti-inflammatory cannabinoid is not completely understood. The goal of this study is to determine the role of adenosine signaling in retinal inflammation and its potential modulation by CBD.
The adenosine receptor (AR) subtypes expressed in rat retinal microglial cells was assessed by quantitative real-time RT-PCR. AR function was determined via in vitro and in vivo inflammatory models. Microglial cells or rats were treated with or without lipopolysaccharide (LPS) in the presence or absence of adenosine, adenosine receptor agonists/antagonists, or CBD. Adenosine uptake and tumor necrosis factor-α (TNF-α) release in cells or in retinas were determined.
Our results showed that A2AARs are abundantly expressed in rat retinal microglial cells. Upon treating the cells or rats with LPS, activation of the A2AAR was the most efficient in mediating AR agonist- or CBD-induced TNF-α inhibition. CBD inhibited adenosine uptake via equilibrative nucleoside transporter 1 and synergistically enhanced adenosine’s TNF-α suppression upon LPS treatment.
These results suggest that the activated A2AAR in the retinal microglial cells plays a major role in anti-inflammation in the retina, and that CBD anti-inflammatory effects are linked to adenosine uptake inhibition.
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