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Updated: Aug 20, 2026
Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model
Published on: January 12, 2022
Synchronous Reactive Oxygen Species Scavenging and Immunomodulation for Autoimmune Uveitis Therapy by a Mannosylated
Jia Shu1, Doudou Ling1, Siqiao Li2
1Ophthalmology Medical Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases, Chongqing Branch (Municipality Division) of National Clinical Research Centre for Ocular Diseases, Chongqing400016, China.
Abstract:
Autoimmune uveitis is a recurrent, vision-threatening inflammatory disease that demands precise and ongoing treatment. However, current therapies have limitations in ocular targeting, in controlling reactive oxygen species (ROS), and in regulating key inflammatory pathways. In this study, we develop a mannosylated biomimetic nanocloak (H-151-Cu/Zn-MOF@LM@Man) that combines active targeting, ROS scavenging, and STING pathway inhibition for a synergistic approach to treating autoimmune uveitis. This nanoplatform consists of a copper-zinc bimetallic metal-organic framework (Cu/Zn-MOF) loaded with the STING antagonist H-151 and coated with a hybrid membrane made from macrophage-derived membranes and mannosylated liposomes (LM@Man). After systemic injection, the nanocloak passively homes to inflamed tissues through membrane camouflage and actively targets mannose receptor-expressing immune cells. It efficiently crosses the blood-retinal barrier (BRB) and accumulates at intraocular lesions. At the inflammation site, the Cu/Zn-MOF core scavenges excess ROS using nanozyme activity. At the same time, H-151 inhibits the STING-TBK1-NF-κB pathway, reshaping macrophage and microglia phenotypes, and restoring immune balance. This closed-loop system effectively reduces inflammatory cytokine production, lessens tissue damage, and enhances therapeutic precision. Overall, this study presents a multifunctional, translatable nanoplatform that enables targeted delivery, redox control, and immune reprogramming─offering a promising strategy for treating autoimmune uveitis and other inflammation-related disorders.
Insights
A novel biomimetic nanocloak effectively targets autoimmune uveitis by scavenging reactive oxygen species (ROS) and inhibiting the STING pathway, offering improved ocular delivery and immune balance.
Area of Science:
- Biomaterials Science
- Immunology
- Ophthalmology
Background:
- Autoimmune uveitis is a vision-threatening inflammatory condition with current treatment limitations.
- Existing therapies struggle with ocular targeting, reactive oxygen species (ROS) control, and inflammatory pathway regulation.
Purpose of the Study:
- To develop a mannosylated biomimetic nanocloak for synergistic treatment of autoimmune uveitis.
- To combine active targeting, ROS scavenging, and STING pathway inhibition in a single nanoplatform.
Main Methods:
- Fabrication of a nanocloak (H-151-Cu/Zn-MOF@LM@Man) using copper-zinc bimetallic metal-organic framework (Cu/Zn-MOF), STING antagonist H-151, and a hybrid membrane of macrophage-derived membranes and mannosylated liposomes.
- Evaluation of the nanocloak's ability to cross the blood-retinal barrier (BRB), target inflamed tissues, scavenge ROS, and inhibit the STING-TBK1-NF-κB pathway.
- Assessment of the nanoplatform's impact on inflammatory cytokine production, tissue damage, and immune cell phenotypes.
Main Results:
- The nanocloak demonstrated efficient accumulation at intraocular lesions after systemic injection.
- The Cu/Zn-MOF core effectively scavenged ROS, while H-151 inhibited the STING pathway, reshaping immune cell phenotypes.
- Significant reduction in inflammatory cytokine production and tissue damage was observed, alongside enhanced therapeutic precision.
Conclusions:
- The developed multifunctional nanoplatform offers targeted delivery, redox control, and immune reprogramming for autoimmune uveitis.
- This approach presents a promising strategy for treating autoimmune uveitis and other inflammation-related disorders.
- The nanocloak system shows potential for enhanced therapeutic precision and reduced side effects.
