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中华眼科医学杂志(电子版) ›› 2025, Vol. 15 ›› Issue (04) : 242 -246. doi: 10.3877/cma.j.issn.2095-2007.2025.04.009

综述

金属离子调控病理性眼部血管生成的研究进展
赵敏, 周宇坤, 刘永瑄, 薛昊天, 沈炜()   
  1. 200433 上海,海军军医大学(第二军医大学)第一附属医院眼科
  • 收稿日期:2025-07-18 出版日期:2025-08-28
  • 通信作者: 沈炜
  • 基金资助:
    国家自然科学基金项目(82271106)

Research progress on metal ion regulation of ocular angiogenesis

Min Zhao, Yukun Zhou, Yongxuan Liu, Haotian Xue, Wei Shen()   

  1. Department of Ophthalmology, Changhai Hospital Naval Medical University (Second Military Medical University), Shanghai 200433, China
  • Received:2025-07-18 Published:2025-08-28
  • Corresponding author: Wei Shen
引用本文:

赵敏, 周宇坤, 刘永瑄, 薛昊天, 沈炜. 金属离子调控病理性眼部血管生成的研究进展[J/OL]. 中华眼科医学杂志(电子版), 2025, 15(04): 242-246.

Min Zhao, Yukun Zhou, Yongxuan Liu, Haotian Xue, Wei Shen. Research progress on metal ion regulation of ocular angiogenesis[J/OL]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2025, 15(04): 242-246.

病理性眼部血管生成是视网膜、脉络膜及角膜等多个部位发生的关键病理过程,会导致玻璃体积血、脉络膜新生血管或角膜混浊,已成为全球不可逆性盲的主要病因之一。血管生成源于已有血管网络的新生分支形成,依赖于内皮细胞激活、迁移及管腔生成等一系列步骤。金属离子是生命体的必需元素,在基础生物过程中发挥着关键作用。金属离子在金属蛋白中主要执行提供结构稳定性、充当酶促反应辅因子及介导电子传递三类功能。其中,铁、铜、锌、钙及锰等五种金属离子对代谢调控发挥着重要作用。近年来,这些金属离子驱动病理性眼部血管生成的多层面机制研究已取得重要进展,并成为该领域研究焦点。该核心调控通路主要涉及铁死亡、铜死亡、锌指转录调控、钙信号级联以及锰酶介导调控。本文中笔者对上述通路及其最新发现进行系统综述,旨在为靶向金属离子稳态通路治疗新生血管性眼病提供新的理论视角与策略启示。

Pathological ocular angiogenesis is a key pathological process occurring in multiple sites including the retina, choroid and cornea, which leading to vitreous hemorrhage, choroidal neovascularization, or corneal opacity, and has become one of the primary causes of irreversible blindness worldwide. Angiogenesis originates from the formation of new branches within existing vascular networks, relying on a series of steps including endothelial cell activation, migration, and lumen formation. Metal ions are essential elements for living organisms, and plays critical roles in almost all fundamental biological processes. Within metalloproteins, metal ions primarily perform three functions: providing structural stability, acting as cofactors for enzymatic reactions, and mediating electron transfer. Among these, five metal ions——iron, copper, zinc, calcium and manganese are particularly crucial for metabolic regulation. Recent years, the significant advances has been witnessed in understanding how these metal ions drive pathological ocular angiogenesis through multi-level mechanisms. Core regulatory pathways involve ferroptosis, cupric death, zinc finger transcription regulation, calcium signaling cascades, and manganese enzyme-mediated control. The aforementioned pathways and their latest discoveries were systematicly reviewed, aiming to provide new theoretical perspectives and strategic insights for targeting metal ion homeostasis pathways in the treatment of neovascular eye diseases.

图1 金属离子代谢在病理性眼部血管生成作用的示意图
图2 湿性年龄相关性黄斑变性患者的光学相干断层扫描血管成像 图A和图B分别示患者右眼和左眼图像,可见右眼黄斑区视网膜增厚、视网膜下高反射渗出灶及视网膜色素上皮层中断;左眼黄斑区视网膜层间水肿、视网膜色素上皮层隆起及视网膜下液性暗区
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