The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid
Regulators, Sirtuin 1 and Liver X Receptor.
Authors Hammer SS, Beli E, Kady N, Wang Q, Wood K, Lydic TA, Malek G, Saban DR, Wang XX,
Hazra S, Levi M, Busik JV, Grant MB
Submitted By Moshe Levi on 8/29/2017
Status Published
Journal EBioMedicine
Year 2017
Date Published 8/1/2017
Volume : Pages 22 : 181 - 190
PubMed Reference 28774737
Abstract Diabetic retinopathy (DR) is a complication secondary to diabetes and is the
number one cause of blindness among working age individuals worldwide. Despite
recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to
be realized. Several clinical trials have highlighted the vital role
dyslipidemia plays in the progression of DR. Additionally, it has recently been
shown that activation of Liver X receptor (LXRa/LXRß) prevents DR in diabetic
animal models. LXRs are nuclear receptors that play key roles in regulating
cholesterol metabolism, fatty acid metabolism and inflammation. In this
manuscript, we show insight into DR pathogenesis by demonstrating an innovative
signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in
modulating retinal cholesterol metabolism and inflammation in the diabetic
retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly
decreased in diabetic human retinal samples and in a type 2 diabetic animal
model. Additionally, activation of LXR restores reverse cholesterol transport,
prevents inflammation, reduces pro-inflammatory macrophages activity and
prevents the formation of diabetes-induced acellular capillaries. Taken
together, the work presented in this manuscript highlights the important role
lipid dysregulation plays in DR progression and offers a novel potential
therapeutic target for the treatment of DR.