Corneal biomechanical cues mediated by PAI-2: the origin of PM2.5-induced corneal disease

The biomechanical signature is directly correlated with the progression of disease in multiple soft tissues. However, their variations and roles, particularly during the initiation period of the disease, remain unclear. Here, we report that PM2.5 exposure induces corneal biomechanical cues alterations prior to corneal injury, as evidenced by increased corneal hysteresis in humans, thickened corneal thickness in rats, and enhanced tensile stress and cortical stiffness in HCECs. Specifically, intracellular PAI-2 is identified as a crucial mediator of the biomechanical responses in HCECs. It modulates PM2.5-induced autophagy and inflammation through a PAI-2/myosin II/F-actin/YAP-positive feedback loop, which ultimately drives HCEC injury. Furthermore, extracellular secretory PAI-2 levels in tears reflect PM2.5-related corneal damage in real time, making it a specific biomarker for the early diagnosis when combined with biomechanical cues. Early intervention for PM2.5-induced ocular damage could be achieved by developing an LNP-siPAI-2 ocular local delivery system targeting intracellular PAI-2. Overall, we propose that biomechanical cues in conjunction with specific biomarkers may serve as targets for the early diagnosis and intervention of soft tissue diseases.

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Publication Details

Journal
EMBO Molecular Medicine
Published
2025-12-01
DOI
https://doi.org/10.1038/s44321-025-00341-0
Primary Topic
Corneal surgery and disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

Corneal biomechanical cues mediated by PAI-2: the origin of PM2.5-induced corneal disease

Lu Chen, Shuai Liu, Hao Ding, Baohua Ji et al.
EMBO Molecular Medicine
Corneal surgery and disorders
article

Corneal biomechanical cues mediated by PAI-2: the origin of PM2.5-induced corneal disease

Lu Chen, Shuai Liu, Hao Ding, Baohua Ji, Zhijian Chen, Guoyong Xie, Zhenwei Qin, Shengjie Hao, Yuzhou Gu, Yili Xu, Feiyin Sheng, Peiwei Xu, Dan Li, Rongrong Chen, Ke Yao, Hong-Ying Jin, Dandan Xu, Na Kong, Kai Su, Qiuli Fu, Lei Zhou
article en

Abstract

The biomechanical signature is directly correlated with the progression of disease in multiple soft tissues. However, their variations and roles, particularly during the initiation period of the disease, remain unclear. Here, we report that PM2.5 exposure induces corneal biomechanical cues alterations prior to corneal injury, as evidenced by increased corneal hysteresis in humans, thickened corneal thickness in rats, and enhanced tensile stress and cortical stiffness in HCECs. Specifically, intracellular PAI-2 is identified as a crucial mediator of the biomechanical responses in HCECs. It modulates PM2.5-induced autophagy and inflammation through a PAI-2/myosin II/F-actin/YAP-positive feedback loop, which ultimately drives HCEC injury. Furthermore, extracellular secretory PAI-2 levels in tears reflect PM2.5-related corneal damage in real time, making it a specific biomarker for the early diagnosis when combined with biomechanical cues. Early intervention for PM2.5-induced ocular damage could be achieved by developing an LNP-siPAI-2 ocular local delivery system targeting intracellular PAI-2. Overall, we propose that biomechanical cues in conjunction with specific biomarkers may serve as targets for the early diagnosis and intervention of soft tissue diseases.

EMBO Molecular MedicineVol. 18(1)
Hong Kong Polytechnic University (HK), Zhejiang Province Institute of Architectural Design and Research (CN), Zhejiang Shuren University (CN), Zhejiang Center for Disease Control and Prevention (CN), He Eye Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Zhejiang University of Technology (CN), Zhejiang University (CN)
National Natural Science Foundation of China, Medical Science and Technology Project of Zhejiang Province, Natural Science Foundation of Zhejiang Province, Science and Technology Program of Zhejiang Province
Openalex Percentile: Top 48%
Corneal surgery and disorders
DOIOpen Access PDFOpenAlex
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