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Z.-H. Song, F. He, Z. Qiao, Y. Njie; Aqueous Humor Outflow Effects of 2-Arachidonylglycerol. Invest. Ophthalmol. Vis. Sci. 2008;49(13):360. doi: https://doi.org/.
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To test the effects of 2-arachidonylglycerol (2-AG), an endocannabinoid, on aqueous humor outflow, to study the cellular mechanisms of 2-AG, and to investigate the possible existence and activity of monoacylgylceride lipase (MGL), a 2-AG metabolic enzyme, in the trabecular meshwork (TM).
The effects of 2-AG on aqueous humor outflow were measured using an anterior segment perfused organ culture model. AlexaFluor 488-labeled phalloidin staining was used to examine actin filament in cultured TM cells. Western blot analysis was used to study the expression of MGL and an enzyme activity assay was performed to measure the enzymatic activity of MGL in TM tissues.
Administration of 10 nM of 2-AG caused a transient enhancement of aqueous humor outflow facility. In the presence of 100 nM of LY2183240, an inhibitor of MGL, the effect of 10nM of 2-AG on outflow facility was prolonged by at least 4 hours. The 2-AG-induced enhancement of outflow facility was blocked by 100 nM SR141716A, a CB1 antagonist, and 100 nM SR144528, a CB2 antagonist. Treatment of TM cells with 10 nM 2-AG plus 100 nM of LY2183240 caused a reduction in actin stress fibers. In Western blot analysis, a 35kD band representing MGL was detected on TM tissues with an anti-MGL antibody. In enzyme activity studies, the enzymatic activity of 2-AG hydrolysis was detected in TM tissues, and this activity was reduced by 70.1 ± 5.3% with the addition of 100nM of LY2183240.
The results from this study demonstrate that administration of 2-AG increases aqueous humor outflow facility. The data also shows that 2-AG -induced enhancement of outflow is mediated through the CB1 and CB2 receptors, possibly with an involvement of changes in actin cytoskeletons in TM cells. In addition, this study demonstrates the existence of functional MGL, an endocannabinoid metabolizing enzyme, in the TM tissues.
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