Neuroprotective and intraocular pressure-lowering effects of (-)Delta9-tetrahydrocannabinol in a rat model of glaucoma.
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.
Crandall
James
J
Department of Ophthalmology, Medical College of Georgia, Augusta, GA 30912, USA.
Matragoon
Suraporn
S
Khalifa
Yousuf M
YM
Borlongan
Caesar
C
Tsai
Nai-Tse
NT
Caldwell
Ruth B
RB
Liou
Gregory I
GI
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002452:Cell Count; D002470:Cell Survival; D004195:Disease Models, Animal; D013759:Dronabinol / Q000627:therapeutic use*; D005901:Glaucoma / Q000188:drug therapy*; D007267:Injections; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000187:drug effects*
D000959:Antihypertensive Agents; D018696:Neuroprotective Agents; D013759:Dronabinol