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

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Neuroprotective effects of topical CB1 agonist WIN 55212-2 on retinal ganglion cells after acute rise in intraocular pressure induced ischemia in rat. / Pinar-Sueiro, Sergio; Zorrilla Hurtado, José Ángel; Veiga-Crespo, Patricia; Sharma, Sansar C; Vecino, Elena.

In: Experimental Eye Research, Vol. 110, 05.2013, p. 55-8.

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TY - JOUR

T1 - Neuroprotective effects of topical CB1 agonist WIN 55212-2 on retinal ganglion cells after acute rise in intraocular pressure induced ischemia in rat

AU - Pinar-Sueiro, Sergio

AU - Zorrilla Hurtado, José Ángel

AU - Veiga-Crespo, Patricia

AU - Sharma, Sansar C

AU - Vecino, Elena

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/5

Y1 - 2013/5

N2 - 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.

AB - 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.

KW - Administration, Topical

KW - Animals

KW - Benzoxazines

KW - Cell Count

KW - Disease Models, Animal

KW - Female

KW - Intraocular Pressure

KW - Morpholines

KW - Naphthalenes

KW - Neuroprotective Agents

KW - Ocular Hypertension

KW - Piperidines

KW - Pyrazoles

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptor, Cannabinoid, CB1

KW - Reperfusion Injury

KW - Retinal Diseases

KW - Retinal Ganglion Cells

KW - Tonometry, Ocular

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.exer.2013.02.009

DO - 10.1016/j.exer.2013.02.009

M3 - Article

VL - 110

SP - 55

EP - 58

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

ER -