Article first published online: 20 AUG 2014
DOI: 10.1111/j.1755-3768.2014.T022.x
2014 Acta Ophthalmologica
Abstract
Purpose Synthetic cannabinoids are emerging novel agents for the treatment of glaucoma. Although increased intraocular pressure (IOP) is a risk factor, associated retinal damage is of prime concern. This study determines the ability of cannabinoids to decrease IOP and confer neuroprotection.
Methods Ocular hypertension was created in Sprague-Dawley (SD) rats by ligating 3 of 4 episcleral veins. IOP increased by at least 5 mm Hg in the operated eye. Cannabinoids, O-1812 (1%) or O-2545 (1%), were administered topically. IOP was measured by Goldmann tonometry at baseline (-30), 0, 30, 60 and 120 min. For neuroprotection experiments: excitotoxic retinal damage was induced by injecting NMDA (2 ul of 10 mM) intravitreally in SD rats. Cannabinoids were injected following NMDA induction. Full-field Electroretinograms were recorded at baseline, 1 wk and 2 wk. ERG a-wave amplitudes are expressed as a percentage of baseline.
Results After treatment with O-2545, IOP was significantly reduced to 11±0.9 mmHg after 60 min and to 12±1.1 mmHg after 120 min compared to baseline of 14±0.6 mmHg (p<0.03, n=6). Similarly, O-1812 treatment reduced IOP to 8.4±1.8 mmHg after 60 min and maintained for up to 120 min (p<0.001, n=6). After 1 wk, NMDA (control) reduced a-wave amplitude by 38±0.1% (p<0.001, n=6) from baseline, O-2545 by 46±0.02% (p<0.001, n=6) and O-1812 by 23±0.1% (p=0.004, n=6). After 2 wks, NMDA further decreased a-wave amplitude by 48±0.1% (p<0.001, n=6), O-2545 by 39±0.03% (p<0.05, n=6) and O-1812 by 8±0.1% (p=0.08, n=6).
Conclusion Topically applied cannabinoids are effective agents that reduce IOP and confer neuroprotection and are prime candidates for potential glaucoma treatment.