Wang Na, Wang Yaqi, Zhang Lei, Yang Wenjing, Fu Songbo
The First Clinical Medical College, Lanzhou University, Lanzhou 730000, China.
Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou 730000, China.
Biomolecules. 2025 May 27;15(6):771. doi: 10.3390/biom15060771.
Age-related macular degeneration (AMD), the leading cause of irreversible blindness worldwide, represents a complex neurodegenerative disorder whose pathogenesis remains elusive. At the core of AMD pathophysiology lies the retinal pigment epithelium (RPE), whose epithelial-mesenchymal transition (EMT) has emerged as a critical pathological mechanism driving disease progression. This transformative process, characterized by RPE cell dedifferentiation and subsequent extracellular matrix remodeling, is orchestrated through a sophisticated network of molecular interactions and cellular signaling cascades. Our review provides a comprehensive analysis of the molecular landscape underlying RPE EMT in AMD, with particular emphasis on seven interconnected pathological axes: (i) oxidative stress and mitochondrial dysfunction, (ii) hypoxia-inducible factor signaling, (iii) autophagic flux dysregulation, (iv) chronic inflammatory responses, (v) complement system overactivation, (vi) epigenetic regulation through microRNA networks, and (vii) key developmental signaling pathway reactivation. Furthermore, we evaluate emerging therapeutic strategies targeting EMT modulation, providing a comprehensive perspective on potential interventions to halt AMD progression. By integrating current mechanistic insights with therapeutic prospects, this review aims to bridge the gap between fundamental research and clinical translation in AMD management.
年龄相关性黄斑变性（AMD）是全球不可逆性失明的主要原因，是一种复杂的神经退行性疾病，其发病机制尚不清楚。AMD病理生理学的核心是视网膜色素上皮（RPE），其上皮-间质转化（EMT）已成为驱动疾病进展的关键病理机制。这个转化过程的特征是RPE细胞去分化以及随后的细胞外基质重塑，它是通过一个复杂的分子相互作用和细胞信号级联网络来协调的。我们的综述对AMD中RPE EMT的分子格局进行了全面分析，特别强调了七个相互关联的病理轴：（i）氧化应激和线粒体功能障碍，（ii）缺氧诱导因子信号传导，（iii）自噬流失调，（iv）慢性炎症反应，（v）补体系统过度激活，（vi）通过微小RNA网络进行的表观遗传调控，以及（vii）关键发育信号通路的重新激活。此外，我们评估了针对EMT调节的新兴治疗策略，为阻止AMD进展的潜在干预措施提供了全面的视角。通过将当前的机制见解与治疗前景相结合，本综述旨在弥合AMD管理中基础研究与临床转化之间的差距。
