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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+Show Affiliations

    ,

    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
    Dronabinol
    Glaucoma
    Injections
    Intraocular Pressure
    Male
    Neuroprotective Agents
    Rats
    Rats, Sprague-Dawley
    Retinal Ganglion Cells

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    17284931

    Citation

    TY - JOUR T1 - Neuroprotective and intraocular pressure-lowering effects of (-)Delta9-tetrahydrocannabinol in a rat model of glaucoma. AU - Crandall,James, AU - Matragoon,Suraporn, AU - Khalifa,Yousuf M, AU - Borlongan,Caesar, AU - Tsai,Nai-Tse, AU - Caldwell,Ruth B, AU - Liou,Gregory I, Y1 - 2007/02/02/ PY - 2006/3/17/received PY - 2006/9/14/accepted PY - 2007/2/2/aheadofprint PY - 2007/2/8/pubmed PY - 2007/5/11/medline PY - 2007/2/8/entrez SP - 69 EP - 75 JF - Ophthalmic research JO - Ophthalmic Res. VL - 39 IS - 2 N2 - 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. SN - 0030-3747 UR - https://www.unboundmedicine.com/medline/citation/17284931/abstract/Neuroprotective_and_Intraocular_Pressure_Lowering_Effects_of____Delta_Tetrahydrocannabinol_in_a_Rat_Model_of_Glaucoma L2 - http://www.karger.com?DOI=10.1159/000099240 ER -