Cannabidiol Preserves Retinal Neurons and Reduces Vascular Permeability in Experimental Diabetes

Abstract

Abstract: : Purpose: Glutamate–induced oxidative stress is likely responsible for the early clinical features of diabetic retinopathy, including increased vascular permeability and neuronal cell injury. We have previously demonstrated the causal effects of reactive oxygen species in stimulating the blood–retinal barrier breakdown in experimental diabetic rats and increasing retinal neuronal cell death in intravitreal N–methyl–D–aspartate (NMDA)–injected rats. We have also shown that the non–psychotropic cannabinoid cannabidiol (CBD) prevents NMDA–induced retinal neuronal cell death. Based on these, we test the hypothesis that CBD reduces vascular permeability and preserves retinal neuronal cells in experimental diabetes. Methods: Experimental diabetes was induced by streptozotocin injection in rats. Vascular permeability was determined by albumin leakage analysis. Apoptosis was determined by terminal dUTP nick end–labeling–horseradish peroxidase (TUNEL–HRP) analysis in whole–mount retinas. Animals were treated with CBD (10 mg/kg of body weight) by intraperitoneal injections every two days. Control animals received vehicle injections. Results: Albumin leakage analysis showed a 4–fold increase in vascular permeability after 2 weeks of diabetes as compared to the non–diabetic control . TUNEL–HRP analysis showed a 7–fold increase in the number of apoptotic retinal cells after 4 weeks of diabetes as compared to the non–diabetic control. CBD treatment reduced vascular permeability by 50% and reduced the number of TUNEL–positive apoptotic cells by 60% as compared to the age–matched diabetic control. Conclusions: CBD preserves retinal neurons and reduces vascular permeability in experimental diabetes. These results suggest that CBD could be a valuable new therapy for the treatment/prevention of diabetes' retinal complications.

Keywords: diabetic retinopathy • neuroprotection • pharmacology