The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor

dc.contributor.authorHammer, Sandra S.
dc.contributor.authorBeli, Eleni
dc.contributor.authorKady, Nermin
dc.contributor.authorWang, Qi
dc.contributor.authorWood, Kiana
dc.contributor.authorLydic, Todd A.
dc.contributor.authorMalek, Goldis
dc.contributor.authorSaban, Daniel R.
dc.contributor.authorWang, Xiaoxin X.
dc.contributor.authorHazra, Sugata
dc.contributor.authorLevi, Moshe
dc.contributor.authorBusik, Julia V.
dc.contributor.authorGrant, Maria B.
dc.contributor.departmentDepartment of Ophthalmology, School of Medicineen_US
dc.date.accessioned2017-08-30T17:36:52Z
dc.date.available2017-08-30T17:36:52Z
dc.date.issued2017-08
dc.description.abstractDiabetic 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 (LXRα/LXRβ) 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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationHammer, S. S., Beli, E., Kady, N., Wang, Q., Wood, K., Lydic, T. A., … Grant, M. B. (2017). The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor. EBioMedicine. https://doi.org/10.1016/j.ebiom.2017.07.008en_US
dc.identifier.urihttps://hdl.handle.net/1805/13976
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.ebiom.2017.07.008en_US
dc.relation.journalEBioMedicineen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourcePublisheren_US
dc.subjectdiabetic retinopathyen_US
dc.subjectdyslipidemiaen_US
dc.subjectliver X receptoren_US
dc.titleThe Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptoren_US
dc.typeArticleen_US
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