Lipid metabolism dysregulation in diabetic retinopathy

• Published in: Journal of lipid research Vol. 62; p. 100017
• Main Author: Busik, Julia V.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2021; Elsevier
• Subjects: animal disease models; antilipemic agents; beta oxidation; blood lipids; cell culture; ceramide; ceramides; cholesterol; clinical trials; diabetic retinopathy; fatty acid; fibrate; high density lipoprotein cholesterol; lipid metabolism disorders; low density lipoprotein cholesterol; mitochondria; omega-3 fatty acids; peroxisome proliferator-activated receptor alpha; protective effect; retina; risk factors; statin; tight junctions; triacylglycerols; triglyceride; triglyceride; mitochondria; RPE; fatty acid; VLC; DR; SC; ceramide; BRB; statin; TJ; cholesterol; tight junctions; ASM; fibrate; Oxidized fatty acids; Eye/retina; Ceramides; Diabetes; diabetic retinopathy; Cholesterol; Omega-3 fatty acids
• ISSN: 0022-2275; 1539-7262; 1539-7262
• DOI: 10.1194/jlr.TR120000981

Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR). This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid-lowering drugs, such as fibrates, omega-3 fatty acids, and statins, for the prevention and treatment of DR. Although several clinical trials demonstrated that treatment with fibrates leads to improvement of DR, there is a dissociation between the protective effects of fibrates in the retina, and the intended blood lipid classes, including plasma triglycerides, total cholesterol, or HDL:LDL cholesterol ratio. Guided by these findings, plasma lipid and lipoprotein-independent mechanisms are addressed based on clinical, cell culture, and animal model studies. Potential retinal-specific effects of fatty acid oxidation products, cholesterol, and ceramide, as well as lipid-independent effects of PPAR alpha activation, are summarized based on the current literature. Overall, this review highlights promising potential of lipid-based treatment strategies further enhanced by the new knowledge of intraretinal lipids and lipoproteins in DR.