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Recreating a human trabecular meshwork outflow system on microfabricated porous structures
Author(s) -
Torrejon Karen Y.,
Pu Dennis,
Bergkvist Magnus,
Danias John,
Sharfstein Susan T.,
Xie Yubing
Publication year - 2013
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.24977
Subject(s) - trabecular meshwork , glaucoma , intraocular pressure , outflow , myocilin , schlemm's canal , in vitro , ophthalmology , pressure sensitive , microbiology and biotechnology , chemistry , biophysics , biology , medicine , materials science , nanotechnology , biochemistry , physics , adhesive , layer (electronics) , meteorology
Glaucoma is the leading cause of irreversible blindness, resulting from an increase in intraocular pressure (IOP). IOP is the only modifiable risk factor of glaucoma and is controlled by the outflow of the aqueous humor through the human trabecular meshwork (HTM). Currently, the lack of a proper in vitro HTM model impedes advances in understanding outflow physiology and discovering effective IOP‐lowering anti‐glaucoma therapeutics. Therefore, we designed and constructed an in vitro HTM model using micropatterned, porous SU‐8 scaffolds, which support cells to recapitulate functional HTM morphology and allow the study of outflow physiology. The pore size of SU‐8 scaffolds, surface coating, cell seeding density, and culture duration were evaluated for HTM cell growth. The bioengineered HTM was characterized by F‐actin staining and immunocytochemistry of HTM markers. A stand‐alone perfusion chamber with an integrated pressure sensing system was further constructed and used for the investigation of the outflow facility of the bioengineered HTM treated with latrunculin B—an IOP lowering agent. Cells in the in vitro model exhibited HTM‐like morphology, expression of α‐smooth muscle actin, myocilin, and αB‐crystallin, outflow characteristics and drug responsiveness. Altogether, we have developed an in vitro HTM model system for understanding HTM cell biology and screening of pharmacological or biological agents that affect trabecular outflow facility, expediting discovery of IOP‐lowering, anti‐glaucoma therapeutics. Biotechnol. Bioeng. 2013;110: 3205–3218. © 2013 Wiley Periodicals, Inc.