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Andrea Unser, Karen Y Torrejon, Feryan Ahmed, Abbey Van Alstyne-Ponce, Brian Murphy; Distinct pharmacological activities between cannabidiol (CBD) and cannabidiol analog (CBDVHS) in a 3D human trabecular meshwork model. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3463.
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© ARVO (1962-2015); The Authors (2016-present)
The eye contains a significant density of cannabinoid receptors, particularly on organs that regulate intraocular pressure (IOP) such as the trabecular meshwork (HTM). We have previously shown in the 3D-HTM™ system that THC lowers IOP by multiple mechanisms, especially by enhancing drainage through the trabecular meshwork. This work led to the current study, in which we examined the impact of CBD and CBDVHS (a bioengineered analog of CBD) on biomarkers associated with inflammation, fibrosis, and tissue elasticity in a normotensive 3D-HTM™model. This study aims to investigate pharmacological differences between CBD and CBDVHS and the physiological implications these have in a 3D HTM™ model.
3D HTM™ normotensive samples from four donors were treated with vehicle, CBD and CBDVHS (0.1, 1, 10 and 100 μΜ, for both) for 4 days. Samples were then assayed for a series of fibrotic markers such as collagen IV, fibronectin, α-smooth muscle actin (αSMA), and paxillin by western blot and immunocytochemistry via confocal microscopy. Statistical analysis (t-test) was conducted using GraphPad Prism.
CBD at 0.1 μM did not significantly change the expression of fibrotic markers (collagen and fibronectin) but induced major F-actin rearrangements while CBDVHS (0.1 μM) significantly decreased these fibrotic markers and F-actin (p<0.05). In addition, a dose of 1 μM CBDVHS significantly decreased αSMA expression (p<0.01) whereas a much larger dose of 100 μM CBD was required to have a significant affect (p<0.05). The changes seen in CBDVHS-treated samples are indicative of cell relaxation, an ideal therapeutic effect.
CBDVHS displays greater potency, at a lower dose, than CBD in decreasing fibrosis and inflammation markers, a finding that is consistent with the use of cannabinoid derivatives to enhance the therapeutic window. These findings suggest that while higher doses of CBD are required for an anti-inflammatory/anti-fibrotic effect, they are also associated with the risk of elevating IOP. Conversely, CBDVHS through greater potency, was able to achieve a better pharmacologic response while lowering the risk of elevating IOP. These data support previous reports that showed CBD could induce ocular hypertension, while CBDVHS does not. Further studies are underway to understand these mechanisms.
This is a 2020 ARVO Annual Meeting abstract.
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