Open AccessA regulatory role for β-adrenergic receptors regarding the resolvin D1 (RvD1) pathway in the diabetic retina
Author(s) -
Haoshen Shi,
Thomas W. Carion,
Youde Jiang,
Adam Chahine,
Jena J. Steinle,
Elizabeth A. Berger
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0185383
Subject(s) - receptor , agonist , diabetic retinopathy , inflammation , pathogenesis , lipid signaling , signal transduction , in vivo , biology , pharmacology , endocrinology , diabetes mellitus , medicine , microbiology and biotechnology , immunology
Diabetic retinopathy is a visually debilitating disease with limited treatment options available. Compound 49b, a β-adrenergic receptor agonist, has been demonstrated to effectively reduce disease pathogenesis associated with diabetic retinopathy. While the exact mechanisms are not fully understood, previous studies have determined that it reduces the pro-inflammatory cytokine, TNF-α, and inhibits apoptosis of the retinal microvasculture. As inflammation becomes more recognized in driving disease pathogenesis, so does the regulation by pro-resolving pathways as therapeutic points of intervention. The current study sought to explore whether Compound 49b had any influence on pro-resolving pathways, thus contributing to improved disease outcome. Using in vivo (animal model of type 1 diabetes) and in vitro (retinal endothelial cells, Müller cells, neutrophils/PMN) techniques, it was determined that high glucose lowers pro-resolving lipid mediator, resolvin D1 (RvD1) levels and differentially alters required enzymes, 5-lipoxygenase (5-LOX), 15-LOX-1 and 15-LOX-2. RvD1 receptors formyl peptide receptor 2 (ALX/FPR2) and G-protein coupled receptor 32 (GPR32) were also downregulated in response to hyperglycemic conditions. Moreover, it was observed that β-adrenergic receptor activation restored high glucose-induced decreases in both enzyme activity and RvD1 levels observed in vivo and in vitro . The current study is the first to describe a regulatory role for β-adrenergic receptors on pro-resolving pathways.