Neuroprotective and intraocular pressure-lowering effects of (-)Δ9-tetrahydrocannabinol in a rat model of glaucoma

James Crandall, Suraporn Matragoon, Yousuf M. Khalifa, Caesar Borlongan, Nai Tse Tsai, Ruth B. Caldwell, Gregory I. Liou

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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 (-)Δ9-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.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalOphthalmic Research
Volume39
Issue number2
DOIs
StatePublished - Mar 2007

Keywords

  • Cannabinoids
  • Ganglion cell
  • Glaucoma
  • Intraocular pressure
  • Neuroprotection

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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