» Articles » PMID: 20806080

Cannabidiol Protects Retinal Neurons by Preserving Glutamine Synthetase Activity in Diabetes

Overview
Journal Mol Vis
Date 2010 Sep 1
PMID 20806080
Citations 11
Authors
Affiliations
Soon will be listed here.
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, Müller 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 Müller 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.

Citing Articles

The pharmacology and therapeutic role of cannabidiol in diabetes.

Zhang J, Lin C, Jin S, Wang H, Wang Y, Du X Exploration (Beijing). 2023; 3(5):20230047.

PMID: 37933286 PMC: 10582612. DOI: 10.1002/EXP.20230047.


Antioxidative and Anti-Inflammatory Properties of Cannabidiol.

Atalay S, Jarocka-Karpowicz I, Skrzydlewska E Antioxidants (Basel). 2019; 9(1).

PMID: 31881765 PMC: 7023045. DOI: 10.3390/antiox9010021.


Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats.

Santiago A, Mori M, Guimaraes F, Milani H, de Oliveira R Neurotox Res. 2018; 35(2):463-474.

PMID: 30430393 DOI: 10.1007/s12640-018-9972-5.


Cannabidiol Treatment Improves Endothelium-Dependent Vasorelaxation in Mesenteric Arteries of Zucker Diabetic Fatty Rats.

Wheal A, Jadoon K, Randall M, OSullivan S Front Pharmacol. 2017; 8:248.

PMID: 28572770 PMC: 5436470. DOI: 10.3389/fphar.2017.00248.


Rod photoreceptors express GPR55 in the adult vervet monkey retina.

Bouskila J, Javadi P, Casanova C, Ptito M, Bouchard J PLoS One. 2013; 8(11):e81080.

PMID: 24244730 PMC: 3828256. DOI: 10.1371/journal.pone.0081080.


References
1.
Gorg B, Wettstein M, Metzger S, Schliess F, Haussinger D . Lipopolysaccharide-induced tyrosine nitration and inactivation of hepatic glutamine synthetase in the rat. Hepatology. 2005; 41(5):1065-73. DOI: 10.1002/hep.20662. View

2.
Belgrave B, Bird K, Chesher G, Jackson D, Lubbe K, Starmer G . The effect of cannabidiol, alone and in combination with ethanol, on human performance. Psychopharmacology (Berl). 1979; 64(2):243-6. DOI: 10.1007/BF00496070. View

3.
Ward M, Jobling A, Kalloniatis M, Fletcher E . Glutamate uptake in retinal glial cells during diabetes. Diabetologia. 2005; 48(2):351-60. DOI: 10.1007/s00125-004-1639-5. View

4.
Marsicano G, Moosmann B, Hermann H, Lutz B, Behl C . Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J Neurochem. 2002; 80(3):448-56. DOI: 10.1046/j.0022-3042.2001.00716.x. View

5.
El-Remessy A, Behzadian M, Abou-Mohamed G, Franklin T, Caldwell R, Caldwell R . Experimental diabetes causes breakdown of the blood-retina barrier by a mechanism involving tyrosine nitration and increases in expression of vascular endothelial growth factor and urokinase plasminogen activator receptor. Am J Pathol. 2003; 162(6):1995-2004. PMC: 1868147. DOI: 10.1016/S0002-9440(10)64332-5. View