With the acceleration of global aging,the incidence of retinal vein occlusion(RVO)has risen markedly.Its pathogenic mechanisms are closely linked to iron dyshomeostasis and microglial polarization and agerelated degen...With the acceleration of global aging,the incidence of retinal vein occlusion(RVO)has risen markedly.Its pathogenic mechanisms are closely linked to iron dyshomeostasis and microglial polarization and agerelated degenerative changes in retinal microvessels.We systematically summarize the regulatory mechanisms of ferroptosis-an iron-dependent,lipid peroxidation-driven form of cell death,and elucidate the central pathway by which iron overload exacerbates retinal injury through the synergy of hypoxia-reoxygenation(H/R).Specifically,iron metabolic imbalance catalyzes the production of reactive oxygen species(ROS)via the Fenton reaction,which drives the polarization of microglia toward the proinflammatory M1 phenotype and activates the acyl-CoA synthetase long-chain family member 4(ACSL4)-mediated lipid peroxidation cascade.This review proposes novel insights for combinatorial therapeutic strategies targeting key ferroptotic pathways(e.g.,the SLC7A11/GPX4 axis)and modulating microglial polarization,while also addressing the translational challenges associated with iron chelators(deferoxamine),lipid peroxidation inhibitors(liproxstatin-1),and targeted delivery systems for RVO.展开更多
基金Supported by the Central High-level Traditional Chinese Medicine Hospital Project,Eye Hospital of China Academy of Chinese Medical Sciences(No.GSP5-96,No.GSP5-83,No.GSP4-02-3)the China Postdoctoral Science Foundation(No.2025M784013)the National Natural Science Foundation of China(No.82474582,No.82174445).
文摘With the acceleration of global aging,the incidence of retinal vein occlusion(RVO)has risen markedly.Its pathogenic mechanisms are closely linked to iron dyshomeostasis and microglial polarization and agerelated degenerative changes in retinal microvessels.We systematically summarize the regulatory mechanisms of ferroptosis-an iron-dependent,lipid peroxidation-driven form of cell death,and elucidate the central pathway by which iron overload exacerbates retinal injury through the synergy of hypoxia-reoxygenation(H/R).Specifically,iron metabolic imbalance catalyzes the production of reactive oxygen species(ROS)via the Fenton reaction,which drives the polarization of microglia toward the proinflammatory M1 phenotype and activates the acyl-CoA synthetase long-chain family member 4(ACSL4)-mediated lipid peroxidation cascade.This review proposes novel insights for combinatorial therapeutic strategies targeting key ferroptotic pathways(e.g.,the SLC7A11/GPX4 axis)and modulating microglial polarization,while also addressing the translational challenges associated with iron chelators(deferoxamine),lipid peroxidation inhibitors(liproxstatin-1),and targeted delivery systems for RVO.
