Cannabinoids: a novel treatment for glaucoma

AbstractPurpose 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.