Liver X Receptor Modulates Diabetic Retinopathy Outcome in a Mouse Model of Streptozotocin-Induced Diabetes

• DOI: 10.2337/db11-1596
• Publication Date: 2012-08-14T02:42:37Z
• Authors: Sugata Hazra; Adil Rasheed; Ashay Bhatwadekar; Xiaoxin Wang; Lynn C. Shaw; Monika Patel; Sergio Caballero; Lilia Magomedova; Nathaniel Solis; Yuanqing Yan; Weidong Wang; Jeffrey S. Thinsc...; Amrisha Verma; Qiuhong Li; Moshe Levi; Carolyn L. Cummins; Maria B. Grant
• Keywords: Liver X receptor

Endothelial progenitor cells (EPCs), critical for mediating vascular repair, are dysfunctional in a hyperglycemic and/or hypercholesterolemic environment. Their dysfunction contributes to the progression of diabetic macro- and microvascular complications. Activation "cholesterol-sensing" nuclear receptors, liver X receptors (LXRα/LXRβ), protects against atherosclerosis by transcriptional regulation genes important promoting cholesterol efflux inhibiting inflammation. We hypothesized that LXR activation with synthetic ligand would correct diabetes-induced EPC improve retinopathy. Studies were performed streptozotocin (STZ)-injected DBA/2J mice fed high-fat Western diet (DBA/STZ/WD) treated agonist GW3965 LXRα(-/-), LXRβ(-/-), LXRα/β(-/-) mice. Retinas evaluated number acellular capillaries glial fibrillary acidic protein (GFAP) immunoreactivity. Bone marrow EPCs analyzed migratory function gene expression. Compared vehicle-treated DBA/STZ/WD mice, showed fewer reduced GFAP These also exhibited enhanced migration restoration inflammatory oxidative stress toward nondiabetic levels. developed similar studies support key role retinal bone associated type 1 diabetes. agonists may represent promising pharmacologic targets correcting retinopathy dysfunction.