Retina Service, Department of Ophthalmology, Mass Eye and Ear, Harvard Medical School, Boston, MA, USA.
Eye (Lond). 2022 Feb;36(2):312-318. doi: 10.1038/s41433-021-01780-y. Epub 2022 Jan 11.
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.
富含脂质的玻璃膜疣是年龄相关性黄斑变性(AMD)的必要条件,是发达国家老年人致盲的主要原因。为了寻找有效的治疗策略,人们提出了这样一个假说,即脂质代谢的改变可能在 AMD 中起致病作用。这一假说得到了以下事实的支持:(1)玻璃膜疣,AMD 的标志性组织病理学特征,由脂质组成;(2)参与脂质稳态的基因的多态性与 AMD 的发生几率增加有关;(3)代谢组学研究表明,AMD 患者的脂质代谢途径中的代谢物发生了改变;(4)血清脂质谱的改变,反映了全身性血脂异常,与 AMD 有关。有强有力的证据表明,他汀类药物是治疗血脂异常和降低心血管疾病风险的药物,可能对某些 AMD 患者群体有治疗作用,但这尚未得到确凿证实。有趣的是,一些研究表明,与心血管风险降低相关的特定血清脂蛋白谱变化(即高密度脂蛋白水平升高)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 中起作用的证据,并就脂质治疗方法在特定 AMD 患者群体中出现之前需要解决的遗留问题提出了我们的观点。