title: Bioengineered glaucomatous 3D human trabecular meshwork as an in vitro disease model.
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. Biotechnol. Bioeng. 2016;113: 1357-1368. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Torrejon
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Papke
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Halman
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Judith
authors.initials: J
authors.lastname: Stolwijk
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Cula N
authors.initials: CN
authors.lastname: Dautriche
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Magnus
authors.initials: M
authors.lastname: Bergkvist
authors.affiliation: Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York.
authors.forename: John
authors.initials: J
authors.lastname: Danias
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Sharfstein
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 Fuller Road, Albany, 12203, New York. YXie@sunypoly.edu.
authors.forename: Yubing
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005901:Glaucoma / Q000473:pathology*; D006801:Humans; D009924:Organ Culture Techniques / Q000379:methods*; D066330:Printing, Three-Dimensional; D023822:Tissue Engineering / Q000295:instrumentation* / Q000379:methods; D054457:Tissue Scaffolds; D014129:Trabecular Meshwork / Q000473:pathology*
keywords: 3D culture; SU-8; intraocular pressure; outflow; steroid-induced glaucoma; trabecular meshwork