NYMC Faculty Publications

Neuroprotective Effects of Topical CB1 Agonist WIN 55212-2 on Retinal Ganglion Cells After Acute Rise in Intraocular Pressure Induced Ischemia in Rat

Author Type(s)

Faculty

DOI

10.1016/j.exer.2013.02.009

Journal Title

Experimental Eye Research

First Page

55

Last Page

58

Document Type

Article

Publication Date

5-1-2013

Department

Ophthalmology

Keywords

Administration, Topical, Animals, Benzoxazines, Cell Count, Disease Models, Animal, Female, Intraocular Pressure, Morpholines, Naphthalenes, Neuroprotective Agents, Ocular Hypertension, Piperidines, Pyrazoles, Rats, Rats, Sprague-Dawley, Receptor, Cannabinoid, CB1, Reperfusion Injury, Retinal Diseases, Retinal Ganglion Cells, Tonometry, Ocular

Disciplines

Medicine and Health Sciences

Abstract

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.

Link to Full Text

Share

COinS