Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma

Diala W. Abu-Hassan, Xinbo Li, Eileen I. Ryan, Ted S. Acott, Mary J. Kelley

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Normally, trabecular meshwork (TM) and Schlemm's canal inner wall endothelial cells within the aqueous humor outflow pathway maintain intraocular pressure within a narrow safe range. Elevation in intraocular pressure, because of the loss of homeostatic regulation by these outflow pathway cells, is the primary risk factor for vision loss due to glaucomatous optic neuropathy. A notable feature associated with glaucoma is outflow pathway cell loss. Using controlled cell loss in ex vivo perfused human outflow pathway organ culture, we developed compelling experimental evidence that this level of cell loss compromises intraocular pressure homeostatic function. This function was restored by repopulation of the model with fresh TM cells. We then differentiated induced pluripotent stem cells (iPSCs) and used them to repopulate this cell depletion model. These differentiated cells (TM-like iPSCs) became similar to TM cells in both morphology and expression patterns. When transplanted, they were able to fully restore intraocular pressure homeostatic function. This successful transplantation of TM-like iPSCs establishes the conceptual feasibility of using autologous stem cells to restore intraocular pressure regulatory function in open-angle glaucoma patients, providing a novel alternative treatment option. Stem Cells 2015;33:751-761

Original languageEnglish (US)
Pages (from-to)751-761
Number of pages11
JournalStem Cells
Volume33
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Autologous stem cell transplantation
  • Cell transplantation
  • Experimental models
  • Induced pluripotent stem cells
  • Somatic stem cells
  • Stem cell transplantation
  • Tissue regeneration
  • Transplantation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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