Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model

Karen Y. Torrejon, Ellen L. Papke, Justin R. Halman, Judith Stolwijk, Cula N. Dautriche, Magnus Bergkvist, John Danias, Susan T. Sharfstein, Yubing Xie

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Intraocular pressure (IOP) is mostly regulated by aqueous humor outflow through the human trabecular meshwork (HTM) and represents the only modifiable risk factor of glaucoma. The lack of IOP-modulating therapeutics that targets HTM underscores the need of engineering HTM for understanding the outflow physiology and glaucoma pathology in vitro. Using a 3D HTM model that allows for regulation of outflow in response to a pharmacologic steroid, a fibrotic state has been induced resembling that of glaucomatous HTM. This disease model exhibits HTM marker expression, ECM overproduction, impaired HTM cell phagocytic activity and outflow resistance, which represent characteristics found in steroid-induced glaucoma. In particular, steroid-induced ECM alterations in the glaucomatous model can be modified by a ROCK inhibitor. Altogether, this work presents a novel in vitro disease model that allows for physiological and pathological studies pertaining to regulating outflow, leading to improved understanding of steroid-induced glaucoma and accelerated discovery of new therapeutic targets.

Original languageEnglish
Pages (from-to)1357-1368
Number of pages12
JournalBiotechnology and Bioengineering
Volume113
Issue number6
DOIs
StatePublished - 1 Jun 2016
Externally publishedYes

Keywords

  • 3D culture
  • Intraocular pressure
  • Outflow
  • SU-8
  • Steroid-induced glaucoma
  • Trabecular meshwork

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