Skowronska-Krawczyk Dorota, Finnemann Silvia C, Grant Maria B, Held Katherine, Hu Zhengping, Lu Yuancheng Ryan, Malek Goldis, Sennlaub Florian, Sparrow Janet, D'Amore Patricia A
Center for Translational Vision Research, School of Medicine, UC Irvine, Irvine, CA, USA.
Department of Biological Sciences, Fordham University, Bronx, NY, USA.
Exp Eye Res. 2025 May;254:110303. doi: 10.1016/j.exer.2025.110303. Epub 2025 Feb 20.
Age-related macular degeneration (AMD) is a complex, multifactorial retinal degenerative disease that is influenced by both genetic and environmental factors. However, the strongest risk factor for AMD is advanced age. Several physiological processes are observed in aging tissues including a low level of chronic inflammation (inflammaging), changed lipid and energy metabolism, and senescence. Nevertheless, whereas everyone ages, only a subset of the population develops AMD. The purpose of this review is to delineate the differences on a cellular and molecular level between natural aging changes and those observed in AMD. We provide a unique perspective on how genetic and environmental components modulate aging in the eye, as well as the specific role of the aging RPE and retina in the pathogenesis of AMD. Topics discussed include the mechanism of aging and its relation to the mechanism of AMD, current animal models that can be used to recapitulate some aspects of the pathology, and potential interventions that shift the balance towards healthy aging and therefore attenuate, prevent or delay the initiation of the disease.
年龄相关性黄斑变性(AMD)是一种复杂的、多因素的视网膜退行性疾病,受遗传和环境因素的影响。然而,AMD最强的风险因素是高龄。在衰老组织中观察到几种生理过程,包括低水平的慢性炎症(炎症衰老)、脂质和能量代谢改变以及细胞衰老。然而,虽然每个人都会衰老,但只有一部分人群会患上AMD。本综述的目的是在细胞和分子水平上描绘自然衰老变化与AMD中观察到的变化之间的差异。我们提供了一个独特的视角,阐述遗传和环境因素如何调节眼部衰老,以及衰老的视网膜色素上皮(RPE)和视网膜在AMD发病机制中的具体作用。讨论的主题包括衰老机制及其与AMD机制的关系、目前可用于概括某些病理方面的动物模型,以及使平衡转向健康衰老从而减轻、预防或延缓疾病发生的潜在干预措施。