Related Experiment Video
Updated: Mar 27, 2026
Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
MiR-93-5p Loaded Lipid Nanoparticles Break the Dry Eye Vicious Cycle via Targeting MAP3K8
Bin Xu1, Xiuna Ji1,2, Longfei Li1
1College of Marine Life Sciences, Ocean University of China, Qingdao 266003, China.
Abstract:
Dry eye disease (DED) is a prevalent ocular disorder characterized by tear film hyperosmolarity and sustained inflammation, which triggers a vicious cycle of corneal damage. Although mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have shown therapeutic potential, their efficacy as a standalone treatment remains limited, and the underlying mechanisms are still unclear, which hinders the development of targeted therapies. Here we demonstrate that limbal MSC-EVs (LMSC-EVs) mitigate hyperosmolar stress (HS)-induced damage in corneal epithelial cells (CECs). This effect was primarily mediated by the delivery of miR-93-5p, which targeted MAP3K8 and suppressed the pro-inflammatory pathway. Notably, superior therapeutic outcomes were achieved using synthetic mannosylerythritol lipid A (MEL-A)-based lipid nanoparticles (LNPs) loaded with miR-93-5p (miR93-LNPs), which significantly alleviated DED symptoms in a mouse model. Mechanistically, we delineated a coherent pathogenic pathway linking HS to CEC inflammation and apoptosis via the TRPV1/ROS/PI3K/Akt/HIF-1α/MAP3K8/p38/NF-κB signaling axis. Our findings provide insights into the molecular mechanisms of DED pathogenesis and highlight miR93-LNPs as a promising cell-free nanotherapeutic strategy for effective DED treatment by breaking its vicious cycle.
Insights
Limbal mesenchymal stem cell-derived extracellular vesicles (LMSC-EVs) deliver miR-93-5p to combat dry eye disease (DED) by targeting inflammation. Synthetic nanoparticles carrying miR-93-5p (miR93-LNPs) offer superior therapeutic outcomes for DED.
Area of Science:
- Ophthalmology
- Regenerative Medicine
- Nanotechnology
Background:
- Dry eye disease (DED) involves hyperosmolarity and inflammation, creating a damaging cycle.
- Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show therapeutic promise for DED, but mechanisms are unclear.
- Current DED treatments have limitations, necessitating novel therapeutic strategies.
Purpose of the Study:
- To investigate the therapeutic potential of limbal MSC-EVs (LMSC-EVs) in mitigating DED.
- To elucidate the molecular mechanisms underlying LMSC-EVs' therapeutic effects in DED.
- To develop and evaluate a novel nanotherapeutic approach for DED treatment.
Main Methods:
- Utilized limbal MSC-EVs (LMSC-EVs) to treat corneal epithelial cells (CECs) under hyperosmolar stress (HS).
- Identified miR-93-5p as the key therapeutic cargo delivered by LMSC-EVs, targeting MAP3K8.
- Developed synthetic mannosylerythritol lipid A (MEL-A)-based lipid nanoparticles (LNPs) loaded with miR-93-5p (miR93-LNPs) for DED treatment in a mouse model.
Main Results:
- LMSC-EVs effectively mitigated HS-induced damage in CECs via miR-93-5p delivery, suppressing inflammation.
- miR93-LNPs demonstrated superior therapeutic efficacy, significantly alleviating DED symptoms in a mouse model.
- Elucidated a detailed pathogenic pathway involving TRPV1/ROS/PI3K/Akt/HIF-1α/MAP3K8/p38/NF-κB in DED.
Conclusions:
- LMSC-EVs and miR93-LNPs represent a promising cell-free nanotherapeutic strategy for DED.
- Targeting the miR-93-5p/MAP3K8 axis offers a novel approach to break the DED vicious cycle.
- Findings provide critical insights into DED pathogenesis and therapeutic interventions.
