CL-EVLPs Promote Corneal Repair in a BAC-Induced Corneal Injury Model via Ocular Microenvironment Reconstruction

  • Invest Ophthalmol Vis Sci. 2026 Mar 2;67(3):4. doi: 10.1167/iovs.67.3.4.
Mengjun Fu  1  2 ,  Dewei Peng  1  3 ,  Yijie Xu  1  4 ,  Yicong Zhang  1  5 ,  Ying Chen  1  6 ,  Qianchun Shao  1  7 ,  Zai-Long Chi  1  8  9
Affiliations
  • 1. State Key Laboratory of Eye Health, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2. https://orcid.org/0000-0002-2736-1952.
  • 3. https://orcid.org/0000-0002-9333-4362.
  • 4. https://orcid.org/0009-0005-6408-8878.
  • 5. https://orcid.org/0009-0000-5298-9752.
  • 6. https://orcid.org/0009-0004-9927-5123.
  • 7. https://orcid.org/0009-0007-4216-3640.
  • 8. National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 9. https://orcid.org/0000-0002-3617-6425.
PMID: 41773773 DOI: 10.1167/iovs.67.3.4
Abstract

Purpose: To investigate the therapeutic potential of Curcuma longa-derived extracellular vesicle-like particles (CL-EVLPs) in a benzalkonium chloride (BAC)-induced corneal injury model.

Methods: CL-EVLPs were isolated via ultracentrifugation and characterized. A murine dry eye model was induced by topical application of BAC. Corneal injury and repair outcomes were assessed using clinical scoring, histopathology, and proteomic analysis. Western blotting and real-time quantitative polymerase chain reaction were conducted to quantify protein or mRNA levels. Bioinformatics analysis was performed using STRING and Cytoscape software.

Results: CL-EVLPs, with a typical saucer- or cup-shaped structure with a PEAK diameter of 104 nm and an average diameter of 138.4 ± 64.3 nm, were efficiently taken up by corneal epithelial cells. Treatment with CL-EVLPs significantly accelerated corneal epithelial repair, reduced pathologic neovascularization, promoted corneal nerve regeneration, and suppressed inflammatory responses in a dry eye mouse model. Proteomic analysis revealed that CL-EVLPs are involved mainly in biological processes such as inflammation, oxidative stress, and immune regulation. Mechanistically, CL-EVLPs upregulated the cornea-specific protein keratin 12 but downregulated the hyperproliferation-associated protein Keratin 10. Additionally, we confirmed that key factors such as proangiogenic VEGFA, proteolytic MMP9, the inflammatory mediators IL-1β and S100A8/A9, and the related transcription factor NF-κB were significantly suppressed, whereas the expression levels of the transcription activator Nrf2 increased.

Conclusions: CL-EVLPs represent a novel natural nanobiologic that restores ocular surface homeostasis, effectively enhancing corneal epithelial regeneration and neural repair in the ocular surface microenvironment. This study provides a foundation for the development of plant-derived EVLPs as a safer and more economical therapeutic strategy for ocular surface disorders.