Ho Sok I, Li Lin, Zuo Sipeng, Tang Jieling, Ye Fuxiang, Gu Ping, Tang Zhimin, Lu Linna
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, P.R. China.
Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, P.R. China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200011, P.R. China.
Acta Biomater. 2025 Aug 9. doi: 10.1016/j.actbio.2025.08.018.
The pathological mechanism of ocular disorders is closely related to dysregulated proliferation or death of ocular cells. Regulated cell death (RCD) is a form of cell death controlled by specific signaling pathways. Diverse types of RCD, such as apoptosis, ferroptosis, autophagy, pyroptosis, and necroptosis, are prevalent in many eye diseases, while the modulation of RCD can alter ocular cell fate and improve disease progression. The pharmacological inducers and inhibitors of RCD have been developed as an emerging approach for ocular therapy. However, the complex ocular anatomy and barriers hinder the efficient use of RCD modulating drugs. Nanomedicine has emerged as a versatile tool in ophthalmic applications for its advanced properties in penetrating ocular barriers, preventing burst effects and rapid inactivation, enabling targeted and controlled release, and facilitating co-delivery of therapeutic agents. Similarly, nanomedicine has been widely explored for its potential in modulating RCD to treat ocular disorders. This review provides a comprehensive overview of the mechanistic roles of five major forms of RCD in eye diseases, summarizes the application of ocular nanomedicine that targets the RCD pathways, and discusses the future prospects of RCD-targeted ocular nanomedicine. It is expected that the elaborately designed RCD-targeted nanomedicine for ocular therapy will play an indispensable role for the establishment of next-generation ocular theranostic nanoplatforms. STATEMENT OF SIGNIFICANCE: Regulated cell death (RCD) significantly manipulates ocular cell fate and is a key driver in the progression of several vision-threatening diseases. However, the complex ocular structures limit the effective use of RCD-regulating therapies. Nanomedicine has emerged as a promising tool to overcome the limitations of the ocular anatomy and precisely modulate RCD, offering new avenues for therapeutic intervention in ocular diseases. In this review, we summarize the mechanistic role of RCD in the pathogenesis of ocular disorders, review current ocular nanomedicines that target the RCD pathway, and discuss the future prospects of RCD-targeted ocular nanomedicine. We aim to provide insights into the potential of targeted nanomedicine in advancing the therapeutics of ocular disorders.
眼部疾病的病理机制与眼部细胞增殖失调或死亡密切相关。调节性细胞死亡（RCD）是一种由特定信号通路控制的细胞死亡形式。多种类型的RCD，如凋亡、铁死亡、自噬、焦亡和坏死性凋亡，在许多眼部疾病中普遍存在，而RCD的调节可以改变眼部细胞命运并改善疾病进展。RCD的药理学诱导剂和抑制剂已被开发为一种新兴的眼部治疗方法。然而，复杂的眼部解剖结构和屏障阻碍了RCD调节药物的有效应用。纳米医学因其在穿透眼部屏障、防止突发效应和快速失活、实现靶向和控释以及促进治疗剂的共递送方面的先进特性，已成为眼科应用中的一种多功能工具。同样，纳米医学在调节RCD以治疗眼部疾病方面的潜力也得到了广泛探索。本综述全面概述了五种主要形式的RCD在眼部疾病中的作用机制，总结了靶向RCD途径的眼部纳米医学的应用，并讨论了靶向RCD的眼部纳米医学的未来前景。预计精心设计的用于眼部治疗的靶向RCD纳米医学将在下一代眼部治疗诊断纳米平台的建立中发挥不可或缺的作用。重要性声明：调节性细胞死亡（RCD）显著影响眼部细胞命运，是几种威胁视力疾病进展的关键驱动因素。然而，复杂的眼部结构限制了RCD调节疗法的有效应用。纳米医学已成为一种有前途的工具，可克服眼部解剖结构的局限性并精确调节RCD，为眼部疾病的治疗干预提供新途径。在本综述中，我们总结了RCD在眼部疾病发病机制中的作用机制，回顾了当前靶向RCD途径的眼部纳米医学，并讨论了靶向RCD的眼部纳米医学的未来前景。我们旨在深入了解靶向纳米医学在推进眼部疾病治疗方面的潜力。
