Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes

A. B. El-Remessy, Y. Khalifa, S. Ola, Ahmed Salah Ibrahim, G. I. Liou

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1487-1495
Number of pages9
JournalMolecular Vision
Volume16
StatePublished - Aug 20 2010

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Cannabidiol
Retinal Neurons
Glutamate-Ammonia Ligase
Tyrosine
Glutamic Acid
Cell Death
DNA Nucleotidylexotransferase
Streptozocin
Sprague Dawley Rats
Retina
Reactive Oxygen Species
Oxidative Stress
Injections

ASJC Scopus subject areas

  • Ophthalmology

Cite this

El-Remessy, A. B., Khalifa, Y., Ola, S., Ibrahim, A. S., & Liou, G. I. (2010). Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes. Molecular Vision, 16, 1487-1495.

Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes. / El-Remessy, A. B.; Khalifa, Y.; Ola, S.; Ibrahim, Ahmed Salah; Liou, G. I.

In: Molecular Vision, Vol. 16, 20.08.2010, p. 1487-1495.

Research output: Contribution to journalArticle

El-Remessy, AB, Khalifa, Y, Ola, S, Ibrahim, AS & Liou, GI 2010, 'Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes', Molecular Vision, vol. 16, pp. 1487-1495.
El-Remessy AB, Khalifa Y, Ola S, Ibrahim AS, Liou GI. Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes. Molecular Vision. 2010 Aug 20;16:1487-1495.
El-Remessy, A. B. ; Khalifa, Y. ; Ola, S. ; Ibrahim, Ahmed Salah ; Liou, G. I. / Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes. In: Molecular Vision. 2010 ; Vol. 16. pp. 1487-1495.
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