Induction of Trabecular Meshwork Cells from Induced Pluripotent Stem Cells

Ding QJ, Zhu W, Cook AC, Anfinson KR, Tucker BA, Kuehn MH

Purpose: 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 co-culture 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 resemble cultured human TM cells morphologically and begin to express many markers of TM cells while ceasing to express pluripotency markers such as Nanog, Oct4 and Sox2. Functionally, these cells develop the ability to phagocytose particles. Finally, exposure to dexamethasone or Phorbol 12-myristate acetate causes a distinct increase in the production and secretion of myocilin and matrix metalloproteinase-3, respectively, behavior characteristic of TM cells. Conclusion: Our data demonstrate that iPSCs can be induced to assume a phenotype that resembles native TM cells in many important aspects. These cells not only represent a valuable research tool, but transplantation into glaucomatous eyes with elevated IOP may also restore function to the TM resulting in reestablishment of IOP.

Invest Ophthalmol Vis Sci.
Publication Date: 
Wed, 10/08/2014
Pubmed ID: