Neuroprotective and Blood-Retinal Barrier-Preserving Effects of Cannabidiol in Experimental Diabetes

Department of Pharmacology and Toxicology, Medical College of Georgia, 1120 15th St., Augusta, GA 30912, USA.
American Journal Of Pathology (Impact Factor: 4.59). 02/2006; 168(1):235-44. DOI: 10.2353/ajpath.2006.050500
Source: PubMed


Diabetic retinopathy is characterized by blood-retinal barrier (BRB) breakdown and neurotoxicity. These pathologies have been associated with oxidative stress and proinflammatory cytokines, which may operate by activating their downstream target p38 MAP kinase. In the present study, the protective effects of a nonpsychotropic cannabinoid, cannabidiol (CBD), were examined in streptozotocin-induced diabetic rats after 1, 2, or 4 weeks. Retinal cell death was determined by terminal dUTP nick-end labeling assay; BRB function by quantifying extravasation of bovine serum albumin-fluorescein; and oxidative stress by assays for lipid peroxidation, dichlorofluorescein fluorescence, and tyrosine nitration. Experimental diabetes induced significant increases in oxidative stress, retinal neuronal cell death, and vascular permeability. These effects were associated with increased levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1 and activation of p38 MAP kinase, as assessed by enzyme-linked immunosorbent assay, immunohistochemistry, and/or Western blot. CBD treatment significantly reduced oxidative stress; decreased the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, and intercellular adhesion molecule-1; and prevented retinal cell death and vascular hyperpermeability in the diabetic retina. Consistent with these effects, CBD treatment also significantly inhibited p38 MAP kinase in the diabetic retina. These results demonstrate that CBD treatment reduces neurotoxicity, inflammation, and BRB breakdown in diabetic animals through activities that may involve inhibition of p38 MAP kinase.

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Available from: Ruth B Caldwell
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    • "We found that by four weeks after onset of diabetes, the number of RGCs was reduced by approximately 40% of the normal number and a gradual decrease in the number of RGCs was demonstrated. Therefore, there is general agreement that all mice strains have shown RGC loss or damage in diabetes [7], [15]–[23]. It is well-known that oxidative stress plays a crucial role in the development of diabetes mellitus [24], [25]. "
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    • "Abu El-Asrar et al. reported that ganglion cells in diabetic retinas express several proapoptotic molecules, such as caspase-3, Fas, and Bax, suggesting that these cells are the most vulnerable population in diabetic retinopathy [9]. Another study showed that neurotoxicity causes permanent impairment of visual function due to cell death of the inner retinal and ganglion cells [10]. Intervention in the apoptosis of ganglion cells may allow us to therapeutically delay or ameliorate neural cell loss in retinal neurodegenerative conditions related to diabetes. "
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