Catalytic neural stem cell exosomes for multi-stage targeting and synergistical therapy of retinal ischemia-reperfusion injury

作者：Weiqiang Yang, Xiaojun Wang, Di-Wei Zheng, Jing Feng, Wenjun Kong, Yue Li, Guanghui Ma, Wei Wei, Yong Tao · 发表于：Cell Reports Medicine · 年份：2025 · DOI：10.1016/j.xcrm.2025.102052 · 被引用次数：10 · 研究领域：Retinal Development and Disorders、Retinal and Optic Conditions、Extracellular vesicles in disease

Neuronal damage of the retina is a leading cause of visual impairment in patients with retinal ischemia-reperfusion injury (RIRI). Building on our clinical and experimental findings, the substantial decrease in catalase activity correlates with increased hydrogen peroxide (H 2 O 2 )-mediated oxidative stress that is primarily localized to the outer nuclear layer (ONL) situated in the posterior segment of the retina. Accordingly, we design a neural stem cell exosome with polylysine (K 10 ) decoration and catalase expression, named CataKNexo, which reaches the ONL and exerts synergistic antioxidant and neuroprotective therapy. Utilizing an in vitro retinal model recapitulating the layered architecture of the retina, we confirm that CataKNexo reaches the ONL through K 10 -mediated transcytosis. In RIRI model mice, CataKNexo prevents the retina from H 2 O 2 -induced cell death, exerts neuroprotection, and restores vision function to near-normal levels. Moreover, CataKNexo shows promising antioxidative, neuroprotective, and safety profiles in RIRI model Bama miniature pigs, highlighting its potential for clinical translation.