AUTHOR=Grether Uwe , Foxton Richard H. , Gruener Sabine , Korn Claudia , Kimbara Atsushi , Osterwald Anja , Zirwes Elisabeth , Uhles Sabine , Thoele Janina , Colé Nadine , Rogers-Evans Mark , Röver Stephan , Nettekoven Matthias , Martin Rainer E. , Adam Jean-Michel , Fingerle Jürgen , Bissantz Caterina , Guba Wolfgang , Alker André , Szczesniak Anna M. , Porter Ross F. , Toguri Tom J. , Revelant Franco , Poirier Agnès , Perret Camille , Winther Lotte , Caruso Antonello , Fezza Filomena , Maccarrone Mauro , Kelly Melanie E. M. , Fauser Sascha , Ullmer Christoph 

TITLE=RG7774 (Vicasinabin), an orally bioavailable cannabinoid receptor 2 (CB2R) agonist, decreases retinal vascular permeability, leukocyte adhesion, and ocular inflammation in animal models

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1426446

DOI=10.3389/fphar.2024.1426446

ISSN=1663-9812

ABSTRACT=First-line pharmacotherapy for diabetic retinopathy (DR) includes regular intravitreal injections with anti-vascular endothelial growth factor (anti-VEGF) therapies. Although effective, intravitreal anti-VEGF injections are highly invasive, and are associated with a high degree of treatment burden, patient anxiety, and an infrequent but serious risk of intraocular inflammation. This preclinical proof-of-concept study shows that RG7774 is a novel, highly selective, and orally bioavailable cannabinoid 2 receptor (CB2R) agonist, with a favorable systemic and ocular pharmacokinetic profile, and beneficial effects on vascular permeability, leukocyte adhesion, and ocular inflammation (key pathological features of DR) in animal models of retinal disease. Results support the development of RG7774 as a potential noninvasive treatment for DR and other retinal diseases with similar pathophysiology.