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

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

  • EMBO Mol Med. 2025 Dec 1. doi: 10.1038/s44321-025-00341-0.
Shengjie Hao # 1,  Guangsong Xie # 2,  Dan Li # 3,  Kexin Su # 4,  Feiyin Sheng 1,  Lu Chen 1,  Yuzhou Gu 1,  Hongying Jin 1,  Yili Xu 1,  Rongrong Chen 1,  Zhenwei Qin 1,  Dandan Xu 5,  Peiwei Xu 5,  Lei Zhou 6,  Na Kong 7,  Hao Ding 8 9,  Zhijian Chen 10,  Shuai Liu 11 12,  Baohua Ji 13,  Ke Yao 14,  Qiuli Fu 15
Affiliations

Affiliations

  • 1 Zhejiang University, Eye Center of Second Affiliated Hospital, School of Medicine; Zhejiang Provincial Key Laboratory of Ophthalmology; Zhejiang Provincial Clinical Research Center for Eye Diseases; Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang Province, China.
  • 2 Biomechanics and Mechanomedicine Laboratory, Department of Engineering Mechanics, Zhejiang University, Hangzhou, Zhejiang Province, China.
  • 3 Hangzhou Heima Eye Clinic, Hangzhou, Zhejiang Province, China.
  • 4 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, China.
  • 5 Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, China.
  • 6 School of Optometry, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong, China.
  • 7 Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
  • 8 Key Laboratory of Environmental Pollution Control Technology of Zhejiang Province, Hangzhou, Zhejiang Province, China.
  • 9 Environmental Science Research & Design Institute of Zhejiang Province, Hangzhou, Zhejiang Province, China.
  • 10 Department of Environmental Health, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang Province, China. [email protected].
  • 11 Zhejiang University, Eye Center of Second Affiliated Hospital, School of Medicine; Zhejiang Provincial Key Laboratory of Ophthalmology; Zhejiang Provincial Clinical Research Center for Eye Diseases; Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang Province, China. [email protected].
  • 12 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, China. [email protected].
  • 13 Biomechanics and Mechanomedicine Laboratory, Department of Engineering Mechanics, Zhejiang University, Hangzhou, Zhejiang Province, China. [email protected].
  • 14 Zhejiang University, Eye Center of Second Affiliated Hospital, School of Medicine; Zhejiang Provincial Key Laboratory of Ophthalmology; Zhejiang Provincial Clinical Research Center for Eye Diseases; Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang Province, China. [email protected].
  • 15 Zhejiang University, Eye Center of Second Affiliated Hospital, School of Medicine; Zhejiang Provincial Key Laboratory of Ophthalmology; Zhejiang Provincial Clinical Research Center for Eye Diseases; Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, Zhejiang Province, China. [email protected].
  • # Contributed equally.
PMID: 41326717 DOI: 10.1038/s44321-025-00341-0
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.

Keywords

Corneal Biomechanics; Corneal Diseases; PM2.5; SerpinB2; Subclinical Stage.

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