Neuroprotective and Intraocular Pressure-Lowering Effects of (-)[Delta]^sup 9^-Tetrahydrocannabinol in a Rat Model of Glaucoma

• Published in: Ophthalmic research Vol. 39; no. 2; p. 69
• Main Authors: Crandall, James, Matragoon, Suraporn, Khalifa, Yousuf M, Borlongan, Caesar, Nai-Tse Tsai, Caldwell, Ruth B, Liou, Gregory I
• Format: Journal Article
• Language: English
• Published: Basel S. Karger AG 01.03.2007
• Subjects: Glaucoma; Ophthalmology
• ISSN: 0030-3747; 1423-0259

In glaucoma, retinal ganglion cell (RGC) death is induced by many risk factors, including ocular hypertension. It has been proposed that glutamate-mediated oxidative stress may also contribute to this RGC death. Cannabinoids are known to possess therapeutic properties including ocular hypotension and antioxidation. In this study, we test the hypothesis that (-)Δ 9 -tetrahydrocannabinol (THC) lowers intraocular pressure (IOP) and prevents RGC death in a rat model of glaucoma. Arat model of experimental glaucoma with chronic, moderately elevated IOP was produced unilaterally by cauterization of episcleral vessels. Rats received weekly injections of THC at a level of 5 mg/kg or vehicle for 20 weeks. IOP of both eyes was measured weekly on anesthetized animals immediately before THC treatment. RGCs were labeled in a retrograde fashion and counted in whole-mounted retinas. IOP was elevated in all operated eyes 1 day after the operation and remained elevated in the vehicle-treated rats throughout 20 weeks. In THC-treated rats, IOP elevation in operated eyes was diminished 2 weeks after operation and remained reduced. IOP in the contralateral control eyes was not affected by THC. In the operated eyes of vehicle-treated animals, there was a loss of ∼50 and 40% of the RGCs in the peripheral and central retina, respectively. The RGC loss in the operated eyes of the THC-treated animals was reduced to 10-20%. These results demonstrate that THC is a neuroprotectant that preserves RGCs in an experimental model of glaucoma, possibly through a reduction in IOP. Copyright © 2007 S. Karger AG, Basel