title: Induction of trabecular meshwork cells from induced pluripotent stem cells.
abstract: OBJECTIVE
  Loss or dysfunction of trabecular meshwork (TM) cells has been associated with the development of pathologically elevated IOP, and it is conceivable that replacement of damaged TM cells could restore function to the TM. We propose that the use of TM-like cells derived from induced pluripotent stem cells (iPSCs) created from a patient's own dermal fibroblasts offers the best solution to this challenge. Here we demonstrate that mouse iPSCs can be induced to differentiate into TM-like cells suitable for autologous transplantation.
  
  
  METHODS
  Directed induction of stem cell differentiation was achieved through coculture of mouse iPSCs with human TM cells for up to 21 days. The resultant TM-like cells (iPSC-TM) were characterized morphologically, immunohistochemically, and functionally.
  
  
  RESULTS
  The iPSC-TM cells closely resembled cultured human TM cells morphologically and began to express many markers of TM cells while ceasing to express pluripotency markers such as Nanog, Oct4, and Sox2. Functionally, these cells developed the ability to phagocytose particles. Finally, exposure to dexamethasone or phorbol 12-myristate acetate caused a distinct increase in the production and secretion of myocilin and matrix metalloproteinase-3, respectively, behavior characteristic of TM cells.
  
  
  CONCLUSIONS
  Our data demonstrate that iPSCs can be induced to assume a phenotype that resembles native TM cells in many important aspects. Not only do these cells represent a valuable research tool, but transplantation into glaucomatous eyes with elevated IOP may also restore function to the TM, resulting in re-establishment of IOP.
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States.
authors.forename: Qiong J
authors.initials: QJ
authors.lastname: Ding
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Cook
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Anfinson
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States.
authors.forename: Budd A
authors.initials: BA
authors.lastname: Tucker
authors.affiliation: The Stephen A. Wynn Institute for Vision Research, Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States.
authors.forename: Markus H
authors.initials: MH
authors.lastname: Kuehn
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D005901:Glaucoma / Q000473:pathology* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation*; D051379:Mice; D008822:Mice, Transgenic; D033581:Stem Cell Transplantation / Q000379:methods*; D014129:Trabecular Meshwork / Q000473:pathology*
keywords: glaucoma anterior segment; induced pluripotent stem cells; trabecular meshwork