A regulatory role for β-adrenergic receptors regarding the resolvin D1 (RvD1) pathway in the diabetic retina

PloS One
Haoshen ShiElizabeth A Berger

Abstract

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 ...Continue Reading

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Citations

Aug 1, 2018·Cell Proliferation·Melis ÇolakoğluSreeparna Banerjee
Apr 24, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nora BottenDarlene A Dartt
Oct 16, 2019·Journal of Cellular Physiology·Maria Consiglia TrottaMichele D'Amico
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Feb 14, 2021·Journal of Lipid Research·Julia V Busik
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Methods Mentioned

BETA
lavage
FCS
transfection

Software Mentioned

Prism

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