A tissue-engineered human trabecular meshwork hydrogel for advanced glaucoma disease modeling

Haiyan Li, Tyler Bagué, Alexander Kirschner, Ana N. Strat, Haven Roberts, Robert W. Weisenthal, Alison E. Patteson, Nasim Annabi, W. Daniel Stamer, Preethi S. Ganapathy, Samuel Herberg

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Abnormal human trabecular meshwork (HTM) cell function and extracellular matrix (ECM) remodeling contribute to HTM stiffening in primary open-angle glaucoma (POAG). Most current cellular HTM model systems do not sufficiently replicate the complex native three dimensional (3D) cell-ECM interface, limiting their use for investigating POAG pathology. Tissue-engineered hydrogels are ideally positioned to overcome shortcomings of current models. Here, we report a novel biomimetic HTM hydrogel and test its utility as a POAG disease model. HTM hydrogels were engineered by mixing normal donor-derived HTM cells with collagen type I, elastin-like polypeptide and hyaluronic acid, each containing photoactive functional groups, followed by UV crosslinking. Glaucomatous conditions were induced with dexamethasone (DEX), and effects of the Rho-associated kinase (ROCK) inhibitor Y27632 on cytoskeletal organization and tissue-level function, contingent on HTM cell-ECM interactions, were assessed. DEX exposure increased HTM hydrogel contractility, f-actin and alpha smooth muscle actin abundance and rearrangement, ECM remodeling, and fibronectin deposition - all contributing to HTM hydrogel condensation and stiffening consistent with glaucomatous HTM tissue behavior. Y27632 treatment produced precisely the opposite effects and attenuated the DEX-induced pathologic changes, resulting in HTM hydrogel relaxation and softening. For model validation, confirmed glaucomatous HTM (GTM) cells were encapsulated; GTM hydrogels showed increased contractility, fibronectin deposition, and stiffening vs. normal HTM hydrogels despite reduced GTM cell proliferation. We have developed a biomimetic HTM hydrogel model for detailed investigation of 3D cell-ECM interactions under normal and simulated glaucomatous conditions. Its bidirectional responsiveness to pharmacological challenge and rescue suggests promising potential to serve as screening platform for new POAG treatments with focus on HTM biomechanics.

Original languageEnglish (US)
Article number108472
JournalExperimental Eye Research
StatePublished - Apr 2021


  • Bioengineering
  • ECM mechanics
  • In vitro
  • POAG
  • Tissue stiffening

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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