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Neuroprotective and intraocular pressure-lowering effects of (-)Delta9-tetrahydrocannabinol in a rat model of glaucoma.

Abstract

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 (-)Delta(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 approximately 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.

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  • Publisher Full Text

    • Authors

    Crandall J, Matragoon S, Khalifa YM, Borlongan C, Tsai NT, Caldwell RB, Liou GI

    Institution

    Department of Ophthalmology, Medical College of Georgia, Augusta, GA 30912, USA.

    Source

    Ophthalmic research 39:2 2007 pg 69-75

    MeSH

    Animals
    Antihypertensive Agents
    Cell Count
    Cell Survival
    Disease Models, Animal
    Glaucoma
    Injections
    Intraocular Pressure
    Male
    Neuroprotective Agents
    Rats
    Rats, Sprague-Dawley
    Retinal Ganglion Cells
    Tetrahydrocannabinol

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17284931