Cannabidiol protects retinal neurons by preserving glutamine synthetase activity in diabetes

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

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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 - 2010
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology

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