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Peer-reviewedCC BYBioactive Materials

Microglia-targeted delivery of MCC950 suppresses NLRP3–IL-18-mediated neuroinflammation and retinal injury in retinal vein occlusion

  • Xiao Xue1
  • Huimin Jiang2
  • Weiyue Zhang3
  • Yifan Zhou2
  • Hui Li4
  • Chengbin Zhou5
  • Yuxin Chen4
  • Wei Ma2
  • Yuan Gao6
  • Xunming Ji7
  • Chen Zhou
  • Xuxiang Zhang8
8 affiliations
  1. 1Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China; Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, 100069, China
  2. 2Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, 100069, China
  3. 3Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China
  4. 4Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
  5. 5Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
  6. 6Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
  7. 7Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, 100069, China; Neuro Cardio Vascular Disease Center, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China
  8. 8Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China; Corresponding author. Department of Ophthalmology, Xuanwu Hospital, Capital Medical University, Beijing, 100053, China.
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Abstract

Retinal vein occlusion (RVO) causes retinal ischemia, macular edema, and vision loss, yet current anti-vascular endothelial growth factor (anti-VEGF) therapies primarily limit vascular leakage and leave ischemia-driven neuroinflammation insufficiently controlled. Here, we reveal a critical role for microglia-associated NLRP3–IL-18 signaling in amplifying inflammation during early RVO. Bulk retinal RNA sequencing showed broad innate immune activation, whereas single-cell transcriptomic profiling and spatial protein analysis identified prominent inflammasome-related changes in retinal microglia. Constitutive global deletion of Nlrp3 or Il18 attenuated microglial activation and preserved retinal structure and electrophysiological function. To translate this mechanistic insight into a targeted anti-inflammatory strategy, we engineered MG1-functionalized, MCC950-loaded nanoliposomes for microglia-targeted NLRP3 inhibition. MG1 functionalization promoted preferential nanoparticle uptake by activated microglia and suppressed NLRP3–IL-18 signaling more effectively than free MCC950 or non-targeted nanoliposomes. In experimental RVO, a single intravitreal dose administered 6 h after induction alleviated retinal inflammation and edema while preserving retinal electrophysiological responses. These findings establish microglia-associated NLRP3–IL-18 signaling as a therapeutic target in early RVO and support MG1-MCC950 nanoliposomes as a bioactive nanotherapeutic platform for RVO.

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Cite

BibTeXRIS
BibTeX
@article{xue2026microgliatargeted,
  title = {{Microglia-targeted delivery of MCC950 suppresses NLRP3–IL-18-mediated neuroinflammation and retinal injury in retinal vein occlusion}},
  author = {Xiao Xue and Huimin Jiang and Weiyue Zhang and Yifan Zhou and Hui Li and Chengbin Zhou and Yuxin Chen and Wei Ma and Yuan Gao and Xunming Ji and Chen Zhou and Xuxiang Zhang},
  journal = {Bioactive Materials},
  year = {2026},
  month = oct,
  doi = {10.1016/j.bioactmat.2026.10.022},
  url = {https://doi.org/10.1016/j.bioactmat.2026.10.022},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Microglia-targeted delivery of MCC950 suppresses NLRP3–IL-18-mediated neuroinflammation and retinal injury in retinal vein occlusion
AU  - Xiao Xue
AU  - Huimin Jiang
AU  - Weiyue Zhang
AU  - Yifan Zhou
AU  - Hui Li
AU  - Chengbin Zhou
AU  - Yuxin Chen
AU  - Wei Ma
AU  - Yuan Gao
AU  - Xunming Ji
AU  - Chen Zhou
AU  - Xuxiang Zhang
PY  - 2026
DA  - 2026/10/22
JO  - Bioactive Materials
DO  - 10.1016/j.bioactmat.2026.10.022
UR  - https://doi.org/10.1016/j.bioactmat.2026.10.022
AB  - Retinal vein occlusion (RVO) causes retinal ischemia, macular edema, and vision loss, yet current anti-vascular endothelial growth factor (anti-VEGF) therapies primarily limit vascular leakage and leave ischemia-driven neuroinflammation insufficiently controlled. Here, we reveal a critical role for microglia-associated NLRP3–IL-18 signaling in amplifying inflammation during early RVO. Bulk retinal RNA sequencing showed broad innate immune activation, whereas single-cell transcriptomic profiling and spatial protein analysis identified prominent inflammasome-related changes in retinal microglia. Constitutive global deletion of Nlrp3 or Il18 attenuated microglial activation and preserved retinal structure and electrophysiological function. To translate this mechanistic insight into a targeted anti-inflammatory strategy, we engineered MG1-functionalized, MCC950-loaded nanoliposomes for microglia-targeted NLRP3 inhibition. MG1 functionalization promoted preferential nanoparticle uptake by activated microglia and suppressed NLRP3–IL-18 signaling more effectively than free MCC950 or non-targeted nanoliposomes. In experimental RVO, a single intravitreal dose administered 6 h after induction alleviated retinal inflammation and edema while preserving retinal electrophysiological responses. These findings establish microglia-associated NLRP3–IL-18 signaling as a therapeutic target in early RVO and support MG1-MCC950 nanoliposomes as a bioactive nanotherapeutic platform for RVO.
SN  - 2452-199X
ER  -