金属离子稳态变化与退行性视网膜疾病形成的关系  

The relationship between metal ion homeostasis and the formation of retinal degenerative disease

作　　者：杜雨芝 李根林[1] Du Yuzhi;Li Genlin(Beijing Tongren Eye Center,Beijing Tongren Hospital,Capital Medical University,Beijing Key Laboratory of Ophthalmology and Visual Sciences,Beijing 100730,China)

机构地区：[1]首都医科大学附属北京同仁医院、北京同仁眼科中心,眼科学与视觉科学北京市重点实验室,北京100730

出　　处：《国际眼科纵览》2024年第6期471-475,共5页International Review of Ophthalmology

基　　金：国家自然科学基金(32241001)。

摘　　要：内环境稳态调控是自然生态系统维持动态稳定的重要特性。机体内离子稳态调控异常可引起视网膜组织细胞内蛋白质合成和折叠异常,导致包括视网膜色素变性等多种退行性视网膜疾病的形成。与退行性视网膜疾病相关的金属离子稳态异常表现包括:铁过载引起的脂质过氧化物和活性氧升高,谷胱甘肽和谷胱甘肽过氧化物酶-4水平降低的铁死亡现象;早于细胞凋亡出现的钙离子胞浆和线粒体内异常聚集;内源性锌离子在视网膜色素上皮中的含量随着年龄增长逐渐减少,胞外聚集异常增多等现象,均提示金属离子稳态异常与退行性视网膜疾病形成的可能关系。针对上述机制,多种新型干预方法和技术显示了良好的治疗潜力,包括去铁铜在内的多种铁螯合剂,锌-去铁胺复合物,针对铁死亡使用的基因疗法;d-顺式地尔硫卓和尼伐地平等新型钙离子通道阻滞剂;口服硫酸锌或锌单半胱氨酸以利于恢复锌平衡等。这些策略为干预退行性视网膜疾病提供了新的思路,并为金属离子稳态调控在疾病治疗中的重要作用提供了有力支持。Homeostatic regulation of the internal environment is an important characteristic of natural ecosystems to maintain dynamic stability.Abnormal regulation of ion homeostasis in the body causes abnormal protein synthesis and folding in retinal cells,leading to the formation of various degenerative retinal diseases,including retinitis pigmentosa.Abnormalities in metal ion homeostasis include the“iron death”of elevated lipid peroxides and reactive oxygen species and reduced glutathione and glutathione peroxidase 4 levels due to iron overload;abnormal cytoplasmic and mitochondrial aggregation of calcium that precedes apoptosis;and the decrease of endogenous zinc ions in the retinal pigment epithelium with age,but the increase of extracellular aggregation all suggest a possible relationship between the abnormal homeostasis of metal ions and the formation of retinal degenerative disease.A number of novel interventions and technologies have shown promising therapeutic potential to address these mechanisms,including iron chelators such as“deferiprone”,zinc-desferrioxamine,and gene therapy for iron death,new calcium channel blockers such as D-cis-diltiazem and nivadipine,and the oral administration of zinc sulfate or zinc-monocysteine compound to restore zinc homeostasis.These strategies provide new ideas for intervening in retinal degenerative diseases,providing strong support for the important role of metal ion homeostatic regulation in disease treatment.

关 键 词：金属离子稳态 退行性视网膜疾病 

分 类 号：R774.1[医药卫生—眼科]