Wei Shengsheng, Li Jing, Zhang Yaohua, Li Yong, Wang Yan
Shaanxi Eye Hospital, Xi'an People's Hospital (Xi'an Fourth Hospital), Affiliated People's Hospital of Northwest University, Xi'an, China.
Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Hospital, Tianjin, China.
Eye (Lond). 2025 Jan;39(1):18-27. doi: 10.1038/s41433-024-03371-z. Epub 2024 Oct 8.
Ferroptosis is a type of iron-dependent cell death that differs from apoptosis, necroptosis, autophagy, and other forms of cell death. It is mainly characterized by the accumulation of intracellular lipid peroxides, redox imbalance, and reduced levels of glutathione and glutathione peroxidase 4. Studies have demonstrated that ferroptosis plays an important regulatory role in the occurrence and development of neurodegenerative diseases, stroke, traumatic brain injury, and ischemia-reperfusion injuries. Multiple mechanisms, such as iron metabolism, ferritinophagy, p53, and p62/Keap1/Nrf2, as well as the combination of FSP1/CoQ/NADPH and hepcidin/FPN-1 can alter the vulnerability to ferroptosis. Nevertheless, there has been limited research on the development and management of ferroptosis in the realm of eye disorders, with most studies focusing on retinal conditions such as age-related macular degeneration and retinitis pigmentosa. This review offers a thorough examination of the disruption of iron homeostasis in eye disorders, investigating the underlying mechanisms. We anticipate that the occurrence of ferroptotic cell death will not only establish a fresh field of study in eye diseases, but also present a promising therapeutic target for treating these diseases.
铁死亡是一种铁依赖性细胞死亡,不同于凋亡、坏死性凋亡、自噬和其他形式的细胞死亡。其主要特征是细胞内脂质过氧化物积累、氧化还原失衡以及谷胱甘肽和谷胱甘肽过氧化物酶4水平降低。研究表明,铁死亡在神经退行性疾病、中风、创伤性脑损伤和缺血再灌注损伤的发生和发展中起重要调节作用。多种机制,如铁代谢、铁蛋白自噬、p53和p62/Keap1/Nrf2,以及FSP1/CoQ/NADPH和铁调素/FPN-1的组合,可改变对铁死亡的易感性。然而,在眼部疾病领域,关于铁死亡的发生发展及调控的研究有限,大多数研究集中在年龄相关性黄斑变性和视网膜色素变性等视网膜疾病上。本综述全面审视了眼部疾病中铁稳态的破坏情况,并探究其潜在机制。我们预计,铁死亡性细胞死亡的发生不仅将为眼科疾病建立一个新的研究领域,而且还将为治疗这些疾病提供一个有前景的治疗靶点。