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

El-Remessy AB, Khalifa Y, Ola S, Ibrahim AS, Liou GI - Mol. Vis. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USA. aelremessy@mcg.edu

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.

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Related in: MedlinePlus

Cannabidiol (CBD) prevents Müller cell activation in diabetic animals. Representative images of glial fibrillary acidic protein (GFAP) showing abundant immunofluorescence at the end-feet of the Müller cells and the radial processes stained intensely throughout both the inner and outer retina in the diabetic retinas compared with normal controls. This effect was blocked by treatment with CBD (10 mg/kg/2days, i.p.). Similar results were obtained from five additional animals per group.
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f2: Cannabidiol (CBD) prevents Müller cell activation in diabetic animals. Representative images of glial fibrillary acidic protein (GFAP) showing abundant immunofluorescence at the end-feet of the Müller cells and the radial processes stained intensely throughout both the inner and outer retina in the diabetic retinas compared with normal controls. This effect was blocked by treatment with CBD (10 mg/kg/2days, i.p.). Similar results were obtained from five additional animals per group.

Mentions: Glial activation, as indicated by GFAP, is a common response to stress conditions. There are two types of glial cells in the retina: astrocytes and Müller cells. Therefore, we assessed glial injury in response to the diabetic insult by immunolocalization of GFAP. Astrocytes were notably positively and equally labeled with GFAP in all groups. As shown in Figure 2, only retinas from the diabetic group demonstrated an increase in the intensity of GFAP immunoreactivity in the filaments of Müller cells that extended from the nerve fiber layer and inner plexiform layer into the outer nuclear layer of retina as compared with controls or the CBD-treated group.


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

El-Remessy AB, Khalifa Y, Ola S, Ibrahim AS, Liou GI - Mol. Vis. (2010)

Cannabidiol (CBD) prevents Müller cell activation in diabetic animals. Representative images of glial fibrillary acidic protein (GFAP) showing abundant immunofluorescence at the end-feet of the Müller cells and the radial processes stained intensely throughout both the inner and outer retina in the diabetic retinas compared with normal controls. This effect was blocked by treatment with CBD (10 mg/kg/2days, i.p.). Similar results were obtained from five additional animals per group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2925907&req=5

f2: Cannabidiol (CBD) prevents Müller cell activation in diabetic animals. Representative images of glial fibrillary acidic protein (GFAP) showing abundant immunofluorescence at the end-feet of the Müller cells and the radial processes stained intensely throughout both the inner and outer retina in the diabetic retinas compared with normal controls. This effect was blocked by treatment with CBD (10 mg/kg/2days, i.p.). Similar results were obtained from five additional animals per group.
Mentions: Glial activation, as indicated by GFAP, is a common response to stress conditions. There are two types of glial cells in the retina: astrocytes and Müller cells. Therefore, we assessed glial injury in response to the diabetic insult by immunolocalization of GFAP. Astrocytes were notably positively and equally labeled with GFAP in all groups. As shown in Figure 2, only retinas from the diabetic group demonstrated an increase in the intensity of GFAP immunoreactivity in the filaments of Müller cells that extended from the nerve fiber layer and inner plexiform layer into the outer nuclear layer of retina as compared with controls or the CBD-treated group.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USA. aelremessy@mcg.edu

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.

Show MeSH
Related in: MedlinePlus