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Abhinav Reddy, Sandeep S. Samudre, Alireza Hosseini, Patricia B. Williams, Frank A. Lattanzio, Jr.; Effect of Cannabinoids and MethoxyPolyethylene Glycols on Rat Aqueous Flow Dynamics. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2487.
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Recent studies have demonstrated the efficacy of cannabinoid derivatives and methoxy polyethylene glycols such as MPDTE to reduce intraocular pressure (IOP) and protect retinal ganglionic cells from free radical damage. However, their mechanism of action (MOA) for reducing IOP has not been well studied. This initial study provides insight on their MOA by using a rat model to determine changes in either aqueous humor outflow or aqueous humor production.
A Zeiss fluorescent microscope was fitted with a stage and special optics to permit in vivo imaging of the rat anterior chamber using an Olympus DP71 camera. Rats were sedated, baseline images of the anterior chamber were collected and then fluorescein was instilled into the rat’s eyes. Rats were allowed to equilibrate for 30 minutes after which another scan was obtained and rats were promptly treated topically with one of the following agents: saline, 1.0% WIN552122 (WIN), 1.0% MPDTE, 0.1% brimonidine or brinzolamide (n = 4 rats per group). Fluorescence images were then obtained at 30 min intervals for 90 min. Resulting scans were analyzed using Metamorph® Software for fluorescein intensity. Data are presented as mean ± SEM.
The greatest reduction in intensity was observed after WIN treatment, a reduction of 73±13%. Brimonidine treatment reduced the intensity by 55±10% followed by MPDTE (42±7%) and brinzolamide (39±4%). After saline treatment, fluorescein intensity in the AC after 90 min was reduced by 31±8%.
Current results suggest that MPDTE like brinzolamide could target aqueous humor production. Similarly, WIN like brimonidine could target aqueous humor outflow. These preliminary results require further experimentation with a larger population of rats to validate the findings. However, this pilot study provides a crucial step forward in elucidating the exact characteristics of WIN and MPDTE MOA.
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