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Peer-reviewedCC BY-NC-NDTranslational vision science & technology

Corneal Stiffening and Hyperosmolar Stress Associate With YAP1/TAZ Activation and Ocular Surface Inflammation in Dry Eye Disease.

  • Yuanyuan Liu1,2
  • Huijuan Chen1,2
  • Kexin Li1,2
  • Haoran Chen1,2
  • Yang Lu1,2
  • Jiaxin Han1,2
  • Bin Lu3
  • Yuzhou Wang1,2
  • Xiujuan Lv1,2
  • Qianwen Gong1,2
  • Liang Hu1,2
  1. 1National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
  2. 2State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
  3. 3Department of Ophthalmology, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, China.
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Abstract

Purpose

To test whether corneal biomechanical remodeling and hyperosmolar stress activate Yes-associated protein 1 (YAP1)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling in dry eye disease (DED), and whether YAP1/transcriptional enhanced associate domain (TEAD) activity is required for ocular surface inflammation in vivo.Methods

A desiccating stress (DS) mouse model was established using low humidity and scopolamine. Tear secretion, corneal fluorescein staining, and stromal stiffness were measured. YAP1/TAZ activity was assessed. DS mice received topical verteporfin (VP) or vehicle control. Human corneal epithelial cells (HCECs) were cultured on substrates of defined stiffness (8, 25, and 50 kPa) and exposed to hyperosmolar medium (500 mOsm) with YAP1 overexpression or knockdown. Public single-cell RNA sequencing data (GSE182582) were reanalyzed.Results

DS reduced tear secretion and increased corneal fluorescein staining and central stromal stiffening. Decreased phosphorylated YAP1 (p-YAP1) and increased nuclear YAP1 indicated pathway activation. Topical VP reduced corneal injury and decreased YAP1, TAZ, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while increasing p-YAP1. In HCECs, substrate stiffness and hyperosmolar stress increased YAP1 activation and inflammatory mediator expression; YAP1 silencing attenuated these responses, whereas YAP1 overexpression enhanced them. Single-cell reanalysis showed inflammatory enrichment in squamous epithelial cells with increased YAP1/WW domain-containing transcription regulator 1 (WWTR1) expression and Hippo pathway activation.Conclusions

Corneal stiffening and hyperosmolar stress are associated with YAP1/TAZ activation and epithelial inflammation in DED. YAP1/TEAD inhibition in DS mice ameliorates corneal injury and inflammatory signaling, supporting functional involvement.Translational relevance

Pharmacologic modulation of YAP1/TEAD signaling may represent a therapeutic strategy for inflammation-dominant DED.

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Cite

BibTeXRIS
BibTeX
@article{liu2026corneal,
  title = {{Corneal Stiffening and Hyperosmolar Stress Associate With YAP1/TAZ Activation and Ocular Surface Inflammation in Dry Eye Disease.}},
  author = {Yuanyuan Liu and Huijuan Chen and Kexin Li and Haoran Chen and Yang Lu and Jiaxin Han and Bin Lu and Yuzhou Wang and Xiujuan Lv and Qianwen Gong and Liang Hu},
  journal = {Translational vision science \& technology},
  year = {2026},
  month = oct,
  doi = {10.1167/tvst.15.10.13},
  url = {https://europepmc.org/article/MED/42867310},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Corneal Stiffening and Hyperosmolar Stress Associate With YAP1/TAZ Activation and Ocular Surface Inflammation in Dry Eye Disease.
AU  - Yuanyuan Liu
AU  - Huijuan Chen
AU  - Kexin Li
AU  - Haoran Chen
AU  - Yang Lu
AU  - Jiaxin Han
AU  - Bin Lu
AU  - Yuzhou Wang
AU  - Xiujuan Lv
AU  - Qianwen Gong
AU  - Liang Hu
PY  - 2026
DA  - 2026/10/01
JO  - Translational vision science & technology
DO  - 10.1167/tvst.15.10.13
UR  - https://europepmc.org/article/MED/42867310
AB  - Purpose  To test whether corneal biomechanical remodeling and hyperosmolar stress activate Yes-associated protein 1 (YAP1)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling in dry eye disease (DED), and whether YAP1/transcriptional enhanced associate domain (TEAD) activity is required for ocular surface inflammation in vivo.Methods  A desiccating stress (DS) mouse model was established using low humidity and scopolamine. Tear secretion, corneal fluorescein staining, and stromal stiffness were measured. YAP1/TAZ activity was assessed. DS mice received topical verteporfin (VP) or vehicle control. Human corneal epithelial cells (HCECs) were cultured on substrates of defined stiffness (8, 25, and 50 kPa) and exposed to hyperosmolar medium (500 mOsm) with YAP1 overexpression or knockdown. Public single-cell RNA sequencing data (GSE182582) were reanalyzed.Results  DS reduced tear secretion and increased corneal fluorescein staining and central stromal stiffening. Decreased phosphorylated YAP1 (p-YAP1) and increased nuclear YAP1 indicated pathway activation. Topical VP reduced corneal injury and decreased YAP1, TAZ, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and interleukin-6 (IL-6), while increasing p-YAP1. In HCECs, substrate stiffness and hyperosmolar stress increased YAP1 activation and inflammatory mediator expression; YAP1 silencing attenuated these responses, whereas YAP1 overexpression enhanced them. Single-cell reanalysis showed inflammatory enrichment in squamous epithelial cells with increased YAP1/WW domain-containing transcription regulator 1 (WWTR1) expression and Hippo pathway activation.Conclusions  Corneal stiffening and hyperosmolar stress are associated with YAP1/TAZ activation and epithelial inflammation in DED. YAP1/TEAD inhibition in DS mice ameliorates corneal injury and inflammatory signaling, supporting functional involvement.Translational relevance  Pharmacologic modulation of YAP1/TEAD signaling may represent a therapeutic strategy for inflammation-dominant DED.
SN  - 2164-2591
ER  -