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F. Stumpff, M. Boxberger, R. Rosenthal, M. Wiederholt, H. Thieme; Synthetic Cannabinoid Receptor Agonists Relax Trabecular Meshwork by Stimulating Maxi-K Channels . Invest. Ophthalmol. Vis. Sci. 2003;44(13):38.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Cannabinoids have been reported to lower intraocular pressure both after systemic and topical application (Eur J Neurosci. 2001 Jan;13(2):409-12) via an unclear mechanism. The purpose of the current study was to determine the effect of synthetic cannabinoid receptor agonists on ionic currents and contractility of trabecular meshwork. Methods: Cultured cells from trabecular meshwork of human donor eyes were studied using the patch-clamp technique (IOVS 1999;40:1404-1417). For contractility experiments, the bovine model was used. (IOVS 2001;42:3193-3201). Results: Patch-clamp experiments: human trabecular meshwork cells were superfused with Ringer's solution containing acetylcholine (5*10-5M) and exposed to the synthetic CB receptor agonist CP 55,940. Outward current level dose-dependently increased to 196 ± 33 % (n=7) (10-6M) and 484 ± 113 % (n=7) (10-5M) of initial level at 100 mV. When cells were exposed to 10–5M CP 55,940 in the presence of the maxi-K channel blocker iberiotoxin (10-7M), no significant change in current occurred (121 ± 28 % (n=8)). When the same protocol was applied using the selective CB1 agonist WIN55212-2 (10-5M), outward current level rose to 205 ± 41 % (n=10); iberiotoxin (10-7M) blocked this response leaving current level unaltered (91 ± 32 %, n=6). Contractility experiments: bovine trabecular meshwork strips were exposed to a carbachol pulse (10-6M) resulting in contraction. When the same pulse was applied in the presence of CP 55,940 (10-5M), only 61 ± 10 %, (n=7) of the original response could be observed. At 10-6M, CP 55,940 reduced contractile response to 83 ± 4 % (n=9), while in two strips contractile force sank more dramatically (22 % and 27 %). Conclusions: Both human and bovine trabecular meshwork cells express CB receptors. Stimulation leads to an opening of maxi-K channels with subsequent hyperpolarisation and relaxation of the tissue, which should enhance aqueous humor outflow.
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