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

## TL;DR

The study shows how PM2.5 exposure affects corneal biomechanics early on, with PAI-2 playing a key role in disease progression and potential for early diagnosis.

## Contribution

The study identifies PAI-2 as a novel mediator of biomechanical responses in PM2.5-induced corneal disease and proposes it as a biomarker for early diagnosis.

## Key findings

- PM2.5 exposure alters corneal biomechanical cues before visible injury occurs.
- PAI-2 regulates cellular responses through a feedback loop involving myosin II, F-actin, and YAP.
- Tear PAI-2 levels reflect PM2.5-induced damage and could serve as an early diagnostic biomarker.

## 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.

The role of biomechanical cues in the progression of PM2.5-induced corneal disease was investigated, and PAI-2 was identified as a key molecule regulating biomechanical responses, with potential as a target for early diagnosis and intervention.

PM2.5 exposure induces corneal biomechanical cues alterations, which precede corneal injury during the subclinical stage.PAI-2 regulates cellular mechanical response and drives PM2.5-related disease progression through a PAI-2/myosin II/F-actin/YAP positive feedback loop.PAI-2 in tears holds potential for mirroring PM2.5-induced disease progression and may be utilized for early diagnosis.LNP-siPAI-2 system can relieve PM2.5-induced ocular damage for early intervention.

PM2.5 exposure induces corneal biomechanical cues alterations, which precede corneal injury during the subclinical stage.

PAI-2 regulates cellular mechanical response and drives PM2.5-related disease progression through a PAI-2/myosin II/F-actin/YAP positive feedback loop.

PAI-2 in tears holds potential for mirroring PM2.5-induced disease progression and may be utilized for early diagnosis.

LNP-siPAI-2 system can relieve PM2.5-induced ocular damage for early intervention.

The role of biomechanical cues in the progression of PM2.5-induced corneal disease was investigated, and PAI-2 was identified as a key molecule regulating biomechanical responses, with potential as a target for early diagnosis and intervention.