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

Research output: Contribution to journalArticle

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.

Details

Authors
External organisations
  • University of the Basque Country
Research areas and keywords

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, Journal Article, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)55-8
Number of pages4
JournalExperimental Eye Research
Volume110
Publication statusPublished - 2013 May
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes