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

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 CBI 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 KW 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 (TM) 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 CBI 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 CBI 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. (C) 2013 Elsevier Ltd. All rights reserved.