Abstract
Lipid-rich drusen are the sine qua non of age-related macular degeneration (AMD), the leading cause of blindness in older adults in the developed world. Efforts directed at uncovering effective therapeutic strategies have led to the hypothesis that altered lipid metabolism may play a pathogenic role in AMD. This hypothesis is supported by the fact that: (1) drusen, the hallmark histopathologic feature of AMD, are composed of lipids, (2) polymorphisms of genes involved in lipid homeostasis are associated with increased odds of AMD, (3) metabolomics studies show that patients with AMD have alterations in metabolites from lipid pathways, and (4) alterations in serum lipid profiles as a reflection of systemic dyslipidemia are associated with AMD. There is strong evidence that statins, which are well described for treating dyslipidemia and reducing risk associated with cardiovascular disease, may have a role for treating certain cohorts of AMD patients, but this has yet to be conclusively proven. Of interest, the specific changes in serum lipoprotein profiles associated with decreased cardiovascular risk (i.e., high HDL levels) have been shown in some studies to be associated with increased risk of AMD. In this review, we highlight the evidence that supports a role for altered lipid metabolism in AMD and provide our perspective regarding the remaining questions that need to be addressed before lipid-based therapies can emerge for specific cohorts of AMD patients.
摘要
富含脂质的玻璃疣是年龄相关性黄斑变性 (AMD) 的重要特征, AMD是发达国家老年人失明的主要原因。为发现有效的治疗策略提出了一个假说, 即脂质代谢的改变可能在AMD中起致病作用。这一假说目前有以下事实支持: (1) 作为AMD标志性组织病理学特征的玻璃疣是由脂质组成, (2) 参与脂质稳态的基因多态性与AMD的患病几率增加有关, (3) 代谢组学研究表明AMD患者的脂质代谢产物发生了改变, 以及4) 反映全身性血脂异常的血脂谱变化与AMD有关。有强有力的证据表明, 他汀类药物可能在治疗某些AMD患者的队列中发挥作用, 但这一观点尚未得到确凿的证明, 且他汀类药物在治疗血脂异常和降低与心血管疾病相关的风险方面得到了证实。有趣的是, 一些研究表明, 血清脂蛋白谱中与心血管风险降低 (即高密度脂蛋白水平) 相关的特定变化与AMD风险增加有关。在这篇综述中, 我们强调了支持脂质代谢改变在AMD中作用的证据, 并就AMD患者特定队列中在脂质治疗前需要解决的问题提出了我们的观点。
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Acknowledgements
The authors thank Danyel Cavazos for assistance with the figures.
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DGV was supported by the Monte J. Wallace Chair in Retina, the Ines and Fred Yeatts Retina Research lab fund, the MLS Foundation, and the American Macular Degeneration Foundation. The funders played no role in study design, data collection and analysis, decision to publish, or preparation of the paper.
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Conceptualization: JBL, DGV. Writing—original draft: JBL, OAH. Writing—review and editing: JBL, OAH, DH, JWM, and DVG. Supervision: JBL, DGV. Funding acquisition: DGV.
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Lin, J.B., Halawa, O.A., Husain, D. et al. Dyslipidemia in age-related macular degeneration. Eye 36, 312–318 (2022). https://doi.org/10.1038/s41433-021-01780-y
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DOI: https://doi.org/10.1038/s41433-021-01780-y
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