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Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model
Author(s) -
Torrejon Karen Y.,
Papke Ellen L.,
Halman Justin R.,
Stolwijk Judith,
Dautriche Cula N.,
Bergkvist Magnus,
Danias John,
Sharfstein Susan T.,
Xie Yubing
Publication year - 2016
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.25899
Subject(s) - trabecular meshwork , glaucoma , intraocular pressure , in vitro , outflow , ophthalmology , schlemm's canal , medicine , microbiology and biotechnology , biology , chemistry , biochemistry , physics , meteorology
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. Biotechnol. Bioeng. 2016;113: 1357–1368. © 2015 Wiley Periodicals, Inc.