Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes.

Hdl Handle:
http://hdl.handle.net/10675.2/128
Title:
Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes.
Authors:
El-Remessy, Azza B. ( 0000-0003-4386-1989 ) ; Khalifa, Yousef; Ola, S; Ibrahim, Ahmed S. ( 0000-0001-8480-6252 ) ; Liou, Gregory I.
Abstract:
PURPOSE: We have previously shown that non-psychotropic cannabidiol (CBD) protects retinal neurons in diabetic rats by inhibiting reactive oxygen species and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine synthetase (GS), causing glutamate accumulation and leading to further neuronal cell death. We propose to test the hypothesis that diabetes-induced glutamate accumulation in the retina is associated with tyrosine nitration of GS and that CBD treatment inhibits this process. METHODS: Sprague Dawley rats were made diabetic by streptozotocin injection and received either vehicle or CBD (10 mg/kg/2 days). After eight weeks, retinal cell death, M?�ller cell activation, GS tyrosine nitration, and GS activity were determined. RESULTS: Diabetes causes significant increases in retinal oxidative and nitrative stress compared with controls. These effects were associated with M?�ller cell activation and dysfunction as well as with impaired GS activity and tyrosine nitration of GS. Cannabidiol treatment reversed these effects. Retinal neuronal death was indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls or CBD-treated rats. CONCLUSIONS: These results suggest that diabetes-induced tyrosine nitration impairs GS activity and that CBD preserves GS activity and retinal neurons by blocking tyrosine nitration.
Citation:
Mol Vis. 2010 Aug 4; 16:1487-1495
Issue Date:
31-Aug-2010
URI:
http://hdl.handle.net/10675.2/128
PubMed ID:
20806080
PubMed Central ID:
PMC2925907
Type:
Journal Article; Research Support, Non-U.S. Gov't
ISSN:
1090-0535
Appears in Collections:
Department of Ophthalmology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorEl-Remessy, Azza B.en_US
dc.contributor.authorKhalifa, Yousefen_US
dc.contributor.authorOla, Sen_US
dc.contributor.authorIbrahim, Ahmed S.en_US
dc.contributor.authorLiou, Gregory I.en_US
dc.date.accessioned2010-09-24T22:03:24Z-
dc.date.available2010-09-24T22:03:24Z-
dc.date.issued2010-08-31en_US
dc.identifier.citationMol Vis. 2010 Aug 4; 16:1487-1495en_US
dc.identifier.issn1090-0535en_US
dc.identifier.pmid20806080en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/128-
dc.description.abstractPURPOSE: We have previously shown that non-psychotropic cannabidiol (CBD) protects retinal neurons in diabetic rats by inhibiting reactive oxygen species and blocking tyrosine nitration. Tyrosine nitration may inhibit glutamine synthetase (GS), causing glutamate accumulation and leading to further neuronal cell death. We propose to test the hypothesis that diabetes-induced glutamate accumulation in the retina is associated with tyrosine nitration of GS and that CBD treatment inhibits this process. METHODS: Sprague Dawley rats were made diabetic by streptozotocin injection and received either vehicle or CBD (10 mg/kg/2 days). After eight weeks, retinal cell death, M?�ller cell activation, GS tyrosine nitration, and GS activity were determined. RESULTS: Diabetes causes significant increases in retinal oxidative and nitrative stress compared with controls. These effects were associated with M?�ller cell activation and dysfunction as well as with impaired GS activity and tyrosine nitration of GS. Cannabidiol treatment reversed these effects. Retinal neuronal death was indicated by numerous terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL)-labeled cells in diabetic rats compared with untreated controls or CBD-treated rats. CONCLUSIONS: These results suggest that diabetes-induced tyrosine nitration impairs GS activity and that CBD preserves GS activity and retinal neurons by blocking tyrosine nitration.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.titleCannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2925907en_US
dc.contributor.corporatenameDepartment of Ophthalmologyen_US
dc.contributor.corporatenameVision Discovery Instituteen_US

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