IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.08-2196 on July 18, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:5526-5531.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-2196
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.08-2196v1
49/12/5526    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Liou, G. I.
Right arrow Articles by Khalifa, Y.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liou, G. I.
Right arrow Articles by Khalifa, Y.

Mediation of Cannabidiol Anti-inflammation in the Retina by Equilibrative Nucleoside Transporter and A2A Adenosine Receptor

Gregory I. Liou,1 John A. Auchampach,2 Cecilia J. Hillard,2 Gu Zhu,1 Bilal Yousufzai,3 Salman Mian,1 Sohail Khan,1 and Yousuf Khalifa1

1From the Department of Ophthalmology and 3The STAR Program, Medical College of Georgia, Augusta, Georgia; and the 2Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin.

PURPOSE. Cannabidiol (CBD), a nonpsychotropic, nontoxic compound has been shown to block diabetes- and endotoxin-induced retinal damage. However, the protective mechanism of this anti-inflammatory cannabinoid is not completely understood. The goal of this study is to determine the role of adenosine signaling in retinal inflammation and its potential modulation by CBD.

METHODS. The adenosine receptor (AR) subtypes expressed in rat retinal microglial cells were assessed by quantitative real-time RT-PCR. AR function was determined via in vitro and in vivo inflammatory models. Microglial cells or rats were treated with or without lipopolysaccharide (LPS) in the presence or absence of adenosine, adenosine receptor agonists/antagonists, or CBD. Adenosine uptake and tumor necrosis factor (TNF)-{alpha} release in cells or in retinas were determined.

RESULTS. The results showed that A2AARs are abundantly expressed in rat retinal microglial cells. When the cells or rats were treated with LPS, activation of the A2AAR was the most efficient in mediating AR agonist- or CBD-induced TNF-{alpha} inhibition. CBD inhibited adenosine uptake via equilibrative nucleoside transporter 1 and synergistically enhanced adenosine’s TNF-{alpha} suppression after treatment with LPS.

CONCLUSIONS. These results suggest that the activated A2AAR in the retinal microglial cells plays a major anti-inflammatory role in the retina and that CBD’s anti-inflammatory effects are linked to the inhibition of adenosine uptake.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Association for Research in Vision and Ophthalmology