Accelerating corneal wound healing using exosome-mediated targeting of NF-κB c-Rel

Inflammation and Regeneration

Research Article

Ruiling Liu¹  Qingguo Ruan¹  Xiaozhen He²  Wenbo Zhao³ 

[1] Eye Institute of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, 266071, Qingdao, China;Eye Institute of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, 266071, Qingdao, China;Eye Institute of Shandong First Medical University, Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), 250021, Jinan, China;Shandong First Medical University (Shandong Academy of Medical Sciences), 250000, Jinan, China;Eye Institute of Shandong First Medical University, State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, 266071, Qingdao, China;

关键词: Corneal wound healing;    Inflammation;    NF-κB;    siRNA;    Exosome;   

DOI  :  10.1186/s41232-023-00260-y

 received in 2022-10-14, accepted in 2023-01-18,  发布年份 2023

来源: Springer

【 摘 要 】

The integrity of the corneal epithelium is essential for the maintenance of the physiological function of the cornea. Studies have found that inflammation greatly delays corneal wound healing. NF-κB c-Rel is preferentially expressed by immune cells and promotes the expression of inflammatory cytokines. In the current study, we sought to investigate whether c-Rel could be used as a potential therapeutic target for treating a corneal injury. Our studies reveal that expressions of c-Rel and its inflammatory targets are significantly increased in the cornea of mice with corneal injury. In addition, we find that c-Rel-deficient mice exhibit accelerated corneal wound healing and reduced expression of inflammatory cytokines. Further studies show that topical treatment on the corneal surface using nano-polymers or exosomes loaded with c-Rel-specific siRNA (siRel) can effectively accelerate regular and diabetic corneal wound healing. More importantly, we find that exosomes, as carriers of siRel, showed better efficacy than nano-polymers in treating corneal injury. We further demonstrate that exosomes secreted by mesenchymal stem cells can efficiently transfer siRNA into macrophages and dendritic cells but not T cells. Taken together, these results indicate that blocking c-Rel may represent an attracting strategy for the treatment of both regular and diabetic corneal injury.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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