《生命科学》 2025, 37(9): 1136-1149

铁死亡在视网膜疾病中的作用机制及治疗策略

袁沈景¹ , 潘霞飞¹ , 纪　猛² , 张　锋² , 吴月红^1,*

¹浙江理工大学生命科学与医药学院，生物化学和分子生物学实验室， 杭州 310018 ²浙江泉生生物工程有限公司，杭州 310018

摘　要：

视网膜疾病是全球不可逆性致盲的主要病因，铁死亡机制的异常激活在其中起关键作用。铁死亡相关病理改变广泛存在于年龄相关性黄斑变性(age-related macular degeneration, AMD)、青光眼、糖尿病视网膜病变(diabetic retinopathy, DR) 和视网膜缺血再灌注损伤等致盲性眼病。深入解析视网膜细胞的铁死亡发生机制，有助于开发靶向治疗策略并完善相关理论体系。本文综述了铁死亡在视网膜疾病中的分子机制，全面总结铁死亡调控通路的新型药物干预策略，并评述人诱导多能干细胞(human induced pluripotent stem cells, hiPSCs) 分化技术在病理机制研究和药物筛选中的应用价值。同时，通过整合基础研究与转化医学成果，本文深入探讨铁死亡靶向治疗在视网膜疾病中的应用潜力，梳理了该领域亟待解决的关键科学问题，以期为推动铁死亡调控药物的研发进程和临床转化应用提供理论依据，最终促进基于铁死亡调控机制的新型诊疗方案在视网膜疾病防治中的应用。

通讯作者：吴月红 , Email:wuyuehong2003@163.com

Mechanism and therapeutic strategies of ferroptosis in retinal diseases

YUAN Shen-Jing¹ , PAN Xia-Fei¹ , JI Meng² , ZHANG Feng² , WU Yue-Hong^1,*

¹Laboratory of Biochemistry and Molecular Biology, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China ²Asia Cell Therapeutics Co. Ltd., Hangzhou 310018, China

Abstract:

Retinal diseases are the leading cause of blindness globally, with dysregulated ferroptosis playing a pivotal role in this process. Ferroptosis-related changes are  observed in major blinding conditions such as agerelated macular degeneration (AMD), glaucoma, diabetic  retinopathy (DR), and retinal ischemia-reperfusion injury.  A comprehensive understanding of the ferroptosis  mechanism in retinal cells is crucial for developing targeted therapeutic strategies and refining the associated theoretical framework. This article reviews molecular mechanisms  of ferroptosis in retinal diseases, summarizes drug interventions targeting ferroptosis pathways, and evaluates the use of human induced pluripotent stem cell (hiPSC) technology for elucidating mechanisms and screening drugs. Furthermore, by integrating insights from basic research and translational medicine, this paper thoroughly explores the potential applications of ferroptosis-targeted therapies in retinal diseases and identifies key scientific challenges in this domain to provide a robust theoretical foundation for accelerating the development and clinical translation of  ferroptosis-targeted drugs. Ultimately, it aims to promote the implementation of innovative diagnostic and therapeutic strategies based on the ferroptosis regulation mechanism for preventing and treating retinal diseases.

Communication Author：WU Yue-Hong , Email:wuyuehong2003@163.com