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年龄相关性黄斑变性:细胞与分子信号传导机制

Age-Related Macular Degeneration: Cellular and Molecular Signaling Mechanisms.

作者信息

Jiang Feipeng, Ma Jier, Lei Chunyan, Zhang Yun, Zhang Meixia

机构信息

Department of Ophthalmology and Research Laboratory of Macular Disease, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Int J Mol Sci. 2025 Jun 26;26(13):6174. doi: 10.3390/ijms26136174.

Abstract

Age-related macular degeneration (AMD) is a progressive retinal disorder and a leading cause of irreversible blindness among elderly individuals, impacting millions of people globally. This review synthesizes the current understanding of the cellular and molecular signaling mechanisms driving AMD, with a focus on the distinct pathophysiological features of dry and wet AMD subtypes. Key mechanisms include oxidative stress, inflammation, lipid metabolism dysregulation, and immune dysregulation, all of which converge on the retinal pigment epithelium (RPE) as a central player in disease initiation and progression. In dry AMD, oxidative damage, mitochondrial dysfunction, and lipofuscin accumulation impair RPE function, contributing to drusen formation and geographic atrophy. In wet AMD, vascular endothelial growth factor-mediated angiogenesis, coupled with inflammation and endothelial metabolic reprogramming, drives choroidal neovascularization. This article integrates findings from multiomics approaches and highlights the potential of artificial intelligence in elucidating AMD pathogenesis and advancing personalized therapies. Future research directions emphasize targeting these molecular pathways to develop innovative treatments, offering hope for improved management of this debilitating condition.

摘要

年龄相关性黄斑变性(AMD)是一种进行性视网膜疾病,是老年人不可逆失明的主要原因,全球影响着数百万人。本综述综合了目前对驱动AMD的细胞和分子信号机制的理解,重点关注干性和湿性AMD亚型的不同病理生理特征。关键机制包括氧化应激、炎症、脂质代谢失调和免疫失调,所有这些机制都汇聚于视网膜色素上皮(RPE),它是疾病发生和发展的核心因素。在干性AMD中,氧化损伤、线粒体功能障碍和脂褐素积累损害RPE功能,导致玻璃膜疣形成和地图样萎缩。在湿性AMD中,血管内皮生长因子介导的血管生成,加上炎症和内皮代谢重编程,驱动脉络膜新生血管形成。本文整合了多组学方法的研究结果,并强调了人工智能在阐明AMD发病机制和推进个性化治疗方面的潜力。未来的研究方向强调针对这些分子途径开发创新疗法,为改善这种使人衰弱的疾病的管理带来希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a53b/12249930/dfe7c3d770cf/ijms-26-06174-g001.jpg

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