title: TGFβ2-induced outflow alterations in a bioengineered trabecular meshwork are offset by a rho-associated kinase inhibitor.
abstract: Members of the transforming growth factor beta (TGFβ) cytokine family have long been associated with affecting several cellular functions, including cell proliferation, differentiation and extracellular matrix (ECM) turnover. Of particular interest to this work, TGFβ2 has been linked to most types of glaucomas as a potential fibrotic agent that can cause elevation of intraocular pressure (IOP). Given that the trabecular meshwork (TM) provides most of aqueous humor outflow resistance in the eye, an in vitro bioengineered human TM (HTM) model has been created and validated by analyzing effects of TGFβ2 on transcellular pressure changes and outflow facility. These changes were correlated with several biological alterations induced by this cytokine, including ECM production and overexpression of HTM-marker myocillin. Furthermore, this TM model has been used to extend current knowledge of gene expression of cytokines involved in TGFβ-induced ECM turnover over time. In particular, the ability for a ROCK-inhibitor to diminish the effect of TGFβ on TM was demonstrated. This work supports the notion that anti-fibrotic activities of ROCK-inhibitors could counteract the elevation of IOP and increased strain observed in glaucomatous TM.
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 fuller road, Albany, New York, 12203, USA.
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, New York, 12203, USA.
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, New York, 12203, USA.
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, New York, 12203, USA.
authors.forename: Magnus
authors.initials: M
authors.lastname: Bergkvist
authors.affiliation: Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, New York, 11203, USA.
authors.forename: John
authors.initials: J
authors.lastname: Danias
authors.affiliation: Colleges of Nanoscale Science and Engineering, SUNY Polytechnic Institute, 257 fuller road, Albany, New York, 12203, USA.
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, New York, 12203, USA.
authors.forename: Yubing
authors.initials: Y
authors.lastname: Xie
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000577:Amides / Q000494:pharmacology*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004852:Epoxy Compounds / Q000737:chemistry; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D008954:Models, Biological; D010477:Perfusion; D011108:Polymers / Q000737:chemistry; D011725:Pyridines / Q000494:pharmacology*; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000099179:Myocilin
chemical_list: D000199:Actins; D000577:Amides; D003598:Cytoskeletal Proteins; D004852:Epoxy Compounds; D005136:Eye Proteins; D006023:Glycoproteins; D011108:Polymers; D011725:Pyridines; D053781:Transforming Growth Factor beta2; D038203:alpha-Crystallin B Chain; D054460:rho-Associated Kinases; D000099179:Myocilin; C541116:ACTA2 protein, human; C059215:CRYAB protein, human; C520895:SU-8 compound; C108830:Y 27632; C515851:ROCK1 protein, human