YAP/TAZ Mediate TGFβ2-Induced Schlemm’s Canal Cell Dysfunction

Haiyan Li, Ayushi Singh, Kristin M. Perkumas, W. Daniel Stamer, Preethi S. Ganapathy, Samuel Herberg

Research output: Contribution to journalArticlepeer-review


PURPOSE. Elevated transforming growth factor beta2 (TGFβ2) levels in the aqueous humor have been linked to glaucomatous outflow tissue dysfunction. Potential mediators of dysfunction are the transcriptional coactivators, Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ). However, the molecular underpinnings of YAP/TAZ modulation in Schlemm’s canal (SC) cells under glaucomatous conditions are not well understood. Here, we investigate how TGFβ2 regulates YAP/TAZ activity in human SC (HSC) cells using biomimetic extracellular matrix hydrogels, and examine whether pharmacological YAP/TAZ inhibition would attenuate TGFβ2-induced HSC cell dysfunction. METHODS. Primary HSC cells were seeded atop photo-cross-linked extracellular matrix hydrogels, made of collagen type I, elastin-like polypeptide and hyaluronic acid, or encapsulated within the hydrogels. HSC cells were induced with TGFβ2 in the absence or presence of concurrent actin destabilization or pharmacological YAP/TAZ inhibition. Changes in actin cytoskeletal organization, YAP/TAZ activity, extracellular matrix production, phospho-myosin light chain levels, and hydrogel contraction were assessed. RESULTS. TGFβ2 significantly increased YAP/TAZ nuclear localization in HSC cells, which was prevented by either filamentous-actin relaxation or depolymerization. Pharmacological YAP/TAZ inhibition using verteporfin without light stimulation decreased fibronectin expression and actomyosin cytoskeletal rearrangement in HSC cells induced by TGFβ2. Similarly, verteporfin significantly attenuated TGFβ2-induced HSC cell-encapsulated hydrogel contraction. CONCLUSIONS. Our data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in HSC cells under simulated glaucomatous conditions and suggest that pharmacological YAP/TAZ inhibition has promising potential to improve outflow tissue dysfunction.

Original languageEnglish (US)
Article number15
JournalInvestigative Ophthalmology and Visual Science
Issue number12
StatePublished - Nov 2022


  • POAG
  • TM stiffness
  • actin cytoskeleton
  • hydrogel
  • mechanotransduction

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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