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CA Rasmussen, BT Gabelt, PL Kaufman; Effect Of Win 55,212-2 On Monkey And Dog Ciliary Muscle In Vitro . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3271.
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Purpose: To investigate the effect of WIN 55,212-2, a cannabinoid that has been reported to lower intraocular pressure (IOP) in primates, and its diluents on monkey and dog isolated ciliary muscle (CM) Methods: CM strips were mounted in a perfusion apparatus and contractile force measured in both the longitudinal (LONG) and circular (CIRC) vectors. CM was perfused with Krebs solution at a rate of 8 or 10 ml/min. Effects of WIN (10µM-40µM) were measured on carbachol (CARB; 1µM) precontracted CM and on CM at resting tension. Effects of different flow rates, DMSO and 2-hydroxypropyl-ß-cylodextrin (HPbCD) concentrations on the CM response were also measured. Results: Monkey CM response (mean±s.e.m.) to CARB was 190±72.1 mg LONG and 112±37.8 mg CIRC (n=6). DMSO decreased the CARB response dose dependently by up to 57±31.8% LONG and 45±11.9% CIRC with 4% DMSO (n=6). The addition of 10 - 40µM WIN to CARB/4% DMSO resulted in minimal changes of up to -9±13% LONG and -9±19% CIRC (n=3) respectively, relative to the CARB/4%DMSO response. CM resting tension in Krebs/4% DMSO was 49.2±25.0 mg LONG and 71.7±16.1mg CIRC (n=3). The addition of 10 - 40µMWIN/4% DMSO resulted in changes of up to -30±22% LONG, and -8±4% CIRC respectively. None of the WIN responses seemed to be dose related. DMSO or HPbCD alone reduced resting tension by 32±32% LONG and 6±3% CIRC (n=10). CM response to CARB/2.25 or 4.5% HPßCD was increased by 7% LONG and 12% CIRC compared to CARB alone. WIN responses with HPßCD were similar to those obtained with DMSO. Dog CM contraction to CARB was much stronger than monkey (269±129.3mg LONG and 178±60.5mg CIRC, n=6). Otherwise the responses to WIN were similar. The optimal fluid flow rates through the chamber were 8 -10ml/min based on responses to CARB. Conclusion: WIN has minimal but variable effects on resting CM tension and CARB stimulated CM contraction. DMSO, and to a lesser extent, HPßCD can alter CARB contraction and resting tension; therefore care must be exercised in interpreting the responses to compounds which must be dissolved in these vehicles. Dog CM contracts strongly to CARB but its use as an alternative to monkey CM must be further evaluated with other compounds.
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