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Y. Njie, Z. Qiao, Z. Xiao, Z.-H. Song; N-Arachidonylethanolamide-Induced Increase in Aqueous Humor Outflow Facility. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3942.
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To study the effects of N-arachidonylethanolamide (anandamide, AEA) on aqueous humor outflow facility and to investigate the possible existence and activity of Fatty Acid Amide Hydrolase (FAAH), an AEA metabolic enzyme in the trabecular meshwork (TM) tissues.
The effects of AEA on aqueous humor outflow facility were measured using a porcine anterior segment perfused organ culture model. Anterior segment explants were mounted on a perfusion chamber and perfused with culture medium at a constant pressure of 7.35 mmHg maintained at 37ºC and 5% CO2. After explants had stabilized, different doses of AEA was administered to the perfusion medium and observed for 5 hrs. To investigate whether FAAH is involved in regulating the effects of AEA on aqueous humor outflow, the anterior segments were pre-treated with the FAAH inhibitor URB597 for 30 minutes prior to AEA application. SR141716A, an antagonist selective for CB1, was administered to determine the involvement of CB1 cannabinoid receptors on the outflow effects of AEA. Western blot analysis was used to study the expression of FAAH and a Thin-Layer Chromatography (TLC) approach was used to measure the enzymatic activity of FAAH on porcine TM tissues.
Administration of 10 nM of AEA caused a transient enhancement [163 ± 18 % of basal (mean ± SE)] of aqueous humor outflow facility. In the presence of 100 nM of URB597, a FAAH inhibitor, the effect of 10 nM of AEA on outflow facility was prolonged by at least 4 hours. The AEA-induced enhancement of outflow facility was blocked by 1 µM of SR141716A, a CB1 antagonist. In Western blot studies, positive signals were detected on porcine TM tissues with an anti-FAAH antibody. In the enzyme activity studies using TM tissues, the rate of hydrolysis of [3H] AEA was protein concentration-dependent. The enzyme activity of AEA hydrolysis was 0.15 ± 0.04 nmol min-1 mg-1 protein (mean ± SE), and this activity was reduced by 86.6 ± 5.3% with the addition of 100 nM of URB597.
The results from this study demonstrate that administration of AEA increases aqueous humor outflow facility and this effect of AEA involves CB1 cannabinoid receptors. In addition, this study demonstrates the existence and the activity of FAAH in the trabecular meshwork tissues, and indictates that this enzyme is involved in regulating the effects of AEA on aqueous humor outflow.
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