The impact of lipids, lipid oxidation, and inflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE.
The impact of lipids, lipid oxidation, and inflammation on AMD, and the potential role of miRNAs on lipid metabolism in the RPE.
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DOI：
10.1016/j.exer.2018.09.023
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发表时间：
2019-04
影响因子：
3.4
通讯作者：
Handa JT
中科院分区：
文献类型：
--
作者：
Jun S;Datta S;Wang L;Pegany R;Cano M;Handa JT
玻璃疣内脂质的积累、高脂饮食的流行病学联系以及与疾病风险相关的脂质代谢基因多态性的鉴定，促使人们对脂质异常在AMD中的作用产生兴趣。尽管进行了深入的研究，但我们对脂质异常如何促进AMD发展的理解仍不清楚。脂质代谢受到严格调节，其失调可引发RPE和布鲁赫膜内的过量脂质积累。黄斑的高氧化应激环境可以促进脂质氧化，损害其原始功能以及产生氧化特异性表位（OSE），除非被中和，否则可以诱导额外有助于AMD进展的不需要的炎症。考虑到脂质代谢和炎症的多个层面，以及同时靶向多个途径的能力，microRNA（miRNAs）已经成为许多年龄相关疾病（包括动脉粥样硬化和阿尔茨海默病）的重要调节剂。这些疾病具有与AMD相似的病因学特征，如富脂沉积、氧化应激和炎症，这表明miRNA可能影响AMD的脂质代谢。在这篇综述中，我们讨论了脂质对AMD病理生物学的贡献，并介绍了miRNA如何在病变发展过程中影响脂质代谢。确定miRNAs如何促进AMD中的脂质积累将有助于确定脂质在AMD中的作用，并为这种神秘疾病开辟新的治疗途径。
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.
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DOI：
10.1073/pnas.0914785107
发表时间：
2010-08-31
影响因子：
11.1
作者：
Conte, Ivan;Carrella, Sabrina;Banfi, Sandro
通讯作者：
Banfi, Sandro
DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
Crabb, JW;Miyagi, M;Hollyfield, JG
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Hollyfield, JG
DOI：
10.1136/bjo.2008.144006
发表时间：
2009-08
期刊：
The British journal of ophthalmology
影响因子：
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作者：
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通讯作者：
Duncan JL
影响因子：
4.4
作者：
Aryal B;Singh AK;Rotllan N;Price N;Fernández-Hernando C
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Fernández-Hernando C
DOI：
10.1136/bjophthalmol-2011-300344
发表时间：
2011-12
期刊：
The British journal of ophthalmology
影响因子：
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作者：
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通讯作者：
Huang JD