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年龄相关性黄斑变性治疗的进展:从传统抗血管内皮生长因子疗法到基因、干细胞和纳米技术领域的新兴疗法。

Advancements in age-related macular degeneration treatment: From traditional anti-VEGF to emerging therapies in gene, stem cell, and nanotechnology.

作者信息

Wang Zhanfei, Zhang Yaqin, Xu Chunxiu, Peng Anna, Qin Huan, Yao Kai

机构信息

Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan 430065, China; College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430065, China.

Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology, Wuhan 430065, China; College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan 430065, China.

出版信息

Biochem Pharmacol. 2025 Jun;236:116902. doi: 10.1016/j.bcp.2025.116902. Epub 2025 Mar 28.

Abstract

Age-related macular degeneration (AMD) is the leading cause of central vision loss in older adults and is projected to affect approximately 400 million individuals worldwide by 2040. Its pathological characteristics include retinal extracellular deposits, such as drusen, which trigger photoreceptor degeneration and damage to the retinal pigment epithelium (RPE), resulting in irreversible vision loss. The pathogenesis of AMD involves genetic, environmental, and aging-related factors. Anti-vascular endothelial growth factor (anti-VEGF) therapy for wet AMD significantly inhibits choroidal neovascularization and delays visual deterioration. However, its high cost, frequent injections, and poor patient compliance limit application, and there remains no effective intervention for dry AMD. In recent years, emerging strategies, such as gene therapy, stem cell therapy, and nanotechnology-based drug delivery systems, offer hope for slowing disease progression by improving targeting, drug stability, and reducing treatment frequency. Nanoparticles, including polymeric and lipid systems, have shown promise for enhancing drug delivery and bioavailability, particularly for dry AMD, where existing therapies are inadequate. These strategies also have the potential to improve patient compliance. This review summarizes AMD epidemiology and examines the limitations of current therapies. It emphasizes the mechanisms and clinical advancements of gene therapy, stem cell therapy, and nanotechnology in AMD treatment. These emerging technologies offer promising opportunities for precision medicine and lay a solid foundation for the future development of multifaceted therapeutic strategies.

摘要

年龄相关性黄斑变性(AMD)是老年人中心视力丧失的主要原因,预计到2040年全球将有大约4亿人受其影响。其病理特征包括视网膜细胞外沉积物,如玻璃膜疣,这些沉积物会引发光感受器变性和视网膜色素上皮(RPE)损伤,导致不可逆的视力丧失。AMD的发病机制涉及遗传、环境和衰老相关因素。湿性AMD的抗血管内皮生长因子(抗VEGF)疗法可显著抑制脉络膜新生血管形成并延缓视力恶化。然而,其高昂的成本、频繁的注射以及患者依从性差限制了其应用,并且干性AMD仍然没有有效的干预措施。近年来,基因治疗、干细胞治疗和基于纳米技术的药物递送系统等新兴策略有望通过改善靶向性、药物稳定性和减少治疗频率来减缓疾病进展。包括聚合物和脂质系统在内的纳米颗粒在增强药物递送和生物利用度方面显示出前景,特别是对于现有疗法不足的干性AMD。这些策略还有可能提高患者依从性。本综述总结了AMD的流行病学,并审视了当前疗法的局限性。它强调了基因治疗、干细胞治疗和纳米技术在AMD治疗中的机制和临床进展。这些新兴技术为精准医学提供了有前景的机会,并为多方面治疗策略的未来发展奠定了坚实基础。

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