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Peer-reviewedCC BY-NC-NDNpj biological physics and mechanics

Microtubule stability modulates Schlemm's canal cell mechanobiology and outflow facility in glaucoma.

  • Haiyan Li1,2
  • Nina Sara Fraticelli-Guzmán1,3,4
  • Kristin M Perkumas5
  • Micah Chrenek1
  • Andrew J Feola1,4,6
  • W Daniel Stamer5
  • C Ross Ethier1,2
6 affiliations
  1. 1Department of Ophthalmology, Emory University, Atlanta, GA USA.
  2. 2Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA USA.
  3. 3George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA USA.
  4. 4Bioengineering Interdisciplinary Program, Georgia Institute of Technology, Atlanta, GA USA.
  5. 5Department of Ophthalmology, Duke University, Durham, NC USA.
  6. 6Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, GA USA.
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Abstract

The inner wall of Schlemm's canal (SC) is a specialized mechanosensitive endothelium in which pore formation is essential for normal conventional aqueous humor outflow and hence intraocular pressure homeostasis, yet the role of microtubule (MT) stability in this process remains poorly understood. Here, using SC cell primary cultures from normal and glaucomatous human eyes as well as mouse whole eye perfusion, we identify MTs as a key component of the mechanotransduction machinery linking the mechanical microenvironment to SC cell biomechanics and conventional outflow. We show that MT stability is modulated by substrate stiffness and diminished in glaucomatous SC cells. MT stabilization suppresses GEF-H1-dependent actomyosin contractility, reduces cellular stiffness, and promotes transcellular pore formation in both normal and glaucomatous SC cells, whereas MT destabilization elicits opposing effects. Consistent with these cellular responses, pharmacological MT stabilization enhances conventional outflow facility in ex vivo mouse eyes. Together, our findings establish MT-dependent cytoskeletal remodeling as a previously unrecognized mechanism linking extracellular mechanical cues to SC biomechanics and transcellular pore formation and highlight MT-associated signaling as a potential therapeutic target for improving conventional outflow in glaucoma.

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Cite

BibTeXRIS
BibTeX
@article{li2026microtubule,
  title = {{Microtubule stability modulates Schlemm's canal cell mechanobiology and outflow facility in glaucoma.}},
  author = {Haiyan Li and Nina Sara Fraticelli-Guzmán and Kristin M Perkumas and Micah Chrenek and Andrew J Feola and W Daniel Stamer and C Ross Ethier},
  journal = {Npj biological physics and mechanics},
  year = {2026},
  month = nov,
  doi = {10.1038/s44341-026-00055-5},
  url = {https://europepmc.org/article/MED/42996666},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Microtubule stability modulates Schlemm's canal cell mechanobiology and outflow facility in glaucoma.
AU  - Haiyan Li
AU  - Nina Sara Fraticelli-Guzmán
AU  - Kristin M Perkumas
AU  - Micah Chrenek
AU  - Andrew J Feola
AU  - W Daniel Stamer
AU  - C Ross Ethier
PY  - 2026
DA  - 2026/11/05
JO  - Npj biological physics and mechanics
DO  - 10.1038/s44341-026-00055-5
UR  - https://europepmc.org/article/MED/42996666
AB  - The inner wall of Schlemm's canal (SC) is a specialized mechanosensitive endothelium in which pore formation is essential for normal conventional aqueous humor outflow and hence intraocular pressure homeostasis, yet the role of microtubule (MT) stability in this process remains poorly understood. Here, using SC cell primary cultures from normal and glaucomatous human eyes as well as mouse whole eye perfusion, we identify MTs as a key component of the mechanotransduction machinery linking the mechanical microenvironment to SC cell biomechanics and conventional outflow. We show that MT stability is modulated by substrate stiffness and diminished in glaucomatous SC cells. MT stabilization suppresses GEF-H1-dependent actomyosin contractility, reduces cellular stiffness, and promotes transcellular pore formation in both normal and glaucomatous SC cells, whereas MT destabilization elicits opposing effects. Consistent with these cellular responses, pharmacological MT stabilization enhances conventional outflow facility in ex vivo mouse eyes. Together, our findings establish MT-dependent cytoskeletal remodeling as a previously unrecognized mechanism linking extracellular mechanical cues to SC biomechanics and transcellular pore formation and highlight MT-associated signaling as a potential therapeutic target for improving conventional outflow in glaucoma.
SN  - 3004-863X
ER  -