Neuroprotective effects of topical CB1 agonist WIN 55212-2 on retinal ganglion cells after acute rise in intraocular pressure induced ischemia in rat

• Published in: Experimental eye research 2013-05, Vol.110, p.55-58
• Main Authors: Pinar-Sueiro, Sergio, Zorrilla Hurtado, José Ángel, Veiga-Crespo, Patricia, Sharma, Sansar C., Vecino, Elena
• Format: Article
• Language: English
• Subjects: acute ischemia; Administration, Topical; AM 251; Animals; Benzoxazines - therapeutic use; cannabinoids; CB1 receptor; Cell Count; Disease Models, Animal; eye drops; Female; Intraocular Pressure; ischemia-reperfusion model; Morpholines - therapeutic use; Naphthalenes - therapeutic use; neuroprotection; Neuroprotective Agents - therapeutic use; Ocular Hypertension - etiology; Piperidines - therapeutic use; Pyrazoles - therapeutic use; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Reperfusion Injury - etiology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Retinal Diseases - etiology; Retinal Diseases - pathology; Retinal Diseases - prevention & control; Retinal Ganglion Cells - drug effects; Retinal Ganglion Cells - pathology; Tonometry, Ocular; WIN 55212-2
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2013.02.009

Neuroprotection in retinal experimental work consists primarily of preventing retinal ganglion cell (RGC) loss after exposure to a hostile event. We have studied the neuroprotective effect on RGCs in an ischemia-reperfusion model by activation of the cannabinoid receptor CB1 using topical application of WIN 55212-2. Intraocular pressure (IOP) was increased by continuous infusion of phosphate buffer saline (PBS) into the anterior chamber of the eye. Mean intraocular pressure was increased up to 88.5 ± 0.29 mm Hg (control normal IOP 15.1 ± 0.25 mm Hg), for 35 min. Animals were distributed in 3 groups. Left eyes underwent acute rise in intraocular pressure. First group was treated with topical Tocrisolve™ 100 in both eyes. Second group was treated with 1% solution of CB1 agonist WIN 55212-2 in both eyes. Third group was treated with WIN 55212-2 1% and CB1 antagonist AM 251 1% solutions in both eyes. Subsequently, RGCs were immunolabeled with Brn3a and automated quantification of retinal mosaics of RGCs were performed. The ischemic damage led to a mean loss in RGC density of 12.33%. After topic administration of WIN 55212-2, mean loss of RGCs was of 2.45%. Co-treatment with CB1 antagonist AM 251 abolished almost completely the neuroprotective effect of WIN 55212-2. Topic 1% WIN 55212-2 showed a neuroprotective effect on RGC degeneration after ischemia-reperfusion without pre-activation of CB1 receptors.