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G. I. Liou, Y. Tang, E. Hanson, S. Matragoon, E. K. Liu, S. Mian, G. Zhu, Y. Khalifa, R. B. Caldwell, A. B. El-Remessy; Neuroprotective Effect of Cannabidiol in Endotoxin-Induced Retinal Inflammation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4954.
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Degenerative retinal diseases such as uveitis, macular degeneration and diabetic retinopathy involve activated microglia and inflammation. Cannabidiol (CBD), a non-psychoactive cannabinoid, has been shown to reduce retinal inflammation and degeneration in an animal model of diabetes. However, the molecular mechanism involved in retinal inflammation and how CBD reduces retinal inflammation and degeneration are not clear. This study is undertaken to test the hypothesis that retinal inflammation and degeneration result from oxidative stress and activation of p38 MAPK, and that CBD reduces retinal inflammation and degeneration by blocking these events.
Uveitis was induced by lipopolysaccharide (LPS) injection. Microglial cells isolated from retinas of newborn rats were cultured. Activation of p38 MAPK and caspase-3 was determined by Western analysis. Reactive oxygen species (ROS) were assayed with 2,7-dichloro-fluorescein diacetate (H2DCFDA) and chemiluminescence. TNF-alpha was determined by ELISA. Cell death was determined by TUNEL and caspase-3 activation analyses.
LPS treatment of rats at 350 microgram/Kg resulted in significant increase in apoptosis in the inner retina, increased levels of ROS, and activation of p38 MAPK. CBD at 5 microgram/Kg blocked these effects. Upon LPS treatment of microglia at 30 ng/ml, ROS were detected within15 min and p38 MAPK activation occurred within 30-60 min. Increases in NO and TNF-alpha formation were detected after 4 hours. CBD at 1 microgram/ml blocked each of these effects and the p38 MAPK inhibitor SB203580 at 10 microMolar partially blocked TNF-alpha formation.
These results suggest that retinal inflammation and degeneration are caused by oxidative stress and activation of p38 MAPK, and that CBD is anti-inflammatory and neuroprotective by inhibiting these events.
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