TY - JOUR
T1 - The impact of lipids, lipid oxidation, and inflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE
AU - Jun, Sujung
AU - Datta, Sayantan
AU - Wang, Lei
AU - Pegany, Roma
AU - Cano, Marisol
AU - Handa, James T.
N1 - Funding Information:
Drs. Jun, Cano, and Handa receive grant support from Bayer Pharmaceutical, Inc. on an unrelated topic. The other authors have no conflicts. BrightFocus Foundation Grant (JTH).EY027691 (JTH), Macular Degeneration Foundation (JTH), Research to Prevent Blindness (Wilmer Eye Institute). Dr. Handa is the Robert Bond Welch Professor.
Funding Information:
Drs. Jun, Cano, and Handa receive grant support from Bayer Pharmaceutical, Inc. on an unrelated topic. The other authors have no conflicts. BrightFocus Foundation Grant (JTH) .
Funding Information:
EY027691 (JTH), Macular Degeneration Foundation (JTH), Research to Prevent Blindness (Wilmer Eye Institute). Dr. Handa is the Robert Bond Welch Professor.
Publisher Copyright:
© 2018
PY - 2019/4
Y1 - 2019/4
N2 - The accumulation of lipids within drusen, the epidemiologic link of a high fat diet, and the identification of polymorphisms in genes involved in lipid metabolism that are associated with disease risk, have prompted interest in the role of lipid abnormalities in AMD. Despite intensive investigation, our understanding of how lipid abnormalities contribute to AMD development remains unclear. Lipid metabolism is tightly regulated, and its dysregulation can trigger excess lipid accumulation within the RPE and Bruch's membrane. The high oxidative stress environment of the macula can promote lipid oxidation, impairing their original function as well as producing oxidation-specific epitopes (OSE), which unless neutralized, can induce unwanted inflammation that additionally contributes to AMD progression. Considering the multiple layers of lipid metabolism and inflammation, and the ability to simultaneously target multiple pathways, microRNA (miRNAs) have emerged as important regulators of many age-related diseases including atherosclerosis and Alzheimer's disease. These diseases have similar etiologic characteristics such as lipid-rich deposits, oxidative stress, and inflammation with AMD, which suggests that miRNAs might influence lipid metabolism in AMD. In this review, we discuss the contribution of lipids to AMD pathobiology and introduce how miRNAs might affect lipid metabolism during lesion development. Establishing how miRNAs contribute to lipid accumulation in AMD will help to define the role of lipids in AMD, and open new treatment avenues for this enigmatic disease.
AB - The accumulation of lipids within drusen, the epidemiologic link of a high fat diet, and the identification of polymorphisms in genes involved in lipid metabolism that are associated with disease risk, have prompted interest in the role of lipid abnormalities in AMD. Despite intensive investigation, our understanding of how lipid abnormalities contribute to AMD development remains unclear. Lipid metabolism is tightly regulated, and its dysregulation can trigger excess lipid accumulation within the RPE and Bruch's membrane. The high oxidative stress environment of the macula can promote lipid oxidation, impairing their original function as well as producing oxidation-specific epitopes (OSE), which unless neutralized, can induce unwanted inflammation that additionally contributes to AMD progression. Considering the multiple layers of lipid metabolism and inflammation, and the ability to simultaneously target multiple pathways, microRNA (miRNAs) have emerged as important regulators of many age-related diseases including atherosclerosis and Alzheimer's disease. These diseases have similar etiologic characteristics such as lipid-rich deposits, oxidative stress, and inflammation with AMD, which suggests that miRNAs might influence lipid metabolism in AMD. In this review, we discuss the contribution of lipids to AMD pathobiology and introduce how miRNAs might affect lipid metabolism during lesion development. Establishing how miRNAs contribute to lipid accumulation in AMD will help to define the role of lipids in AMD, and open new treatment avenues for this enigmatic disease.
KW - Age-related macular degeneration
KW - Inflammation
KW - Lipids
KW - Oxidative stress
KW - Retinal pigmented epithelium
KW - microRNA
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U2 - 10.1016/j.exer.2018.09.023
DO - 10.1016/j.exer.2018.09.023
M3 - Review article
C2 - 30292489
AN - SCOPUS:85054456016
SN - 0014-4835
VL - 181
SP - 346
EP - 355
JO - Experimental eye research
JF - Experimental eye research
ER -