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Advances in the Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells

  • Sarah K. Ohlemacher
  • Kirstin B. Langer
  • Clarisse M. Fligor
  • Elyse M. Feder
  • Michael C. Edler
  • Jason S. MeyerEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1186)

Abstract

Human pluripotent stem cell (hPSC) technology has revolutionized the field of biology through the unprecedented ability to study the differentiation of human cells in vitro. In the past decade, hPSCs have been applied to study development, model disease, develop drugs, and devise cell replacement therapies for numerous biological systems. Of particular interest is the application of this technology to study and treat optic neuropathies such as glaucoma. Retinal ganglion cells (RGCs) are the primary cell type affected in these diseases, and once lost, they are unable to regenerate in adulthood. This necessitates the development of strategies to study the mechanisms of degeneration as well as develop translational therapeutic approaches to treat early- and late-stage disease progression. Numerous protocols have been established to derive RGCs from hPSCs, with the ability to generate large populations of human RGCs for translational applications. In this review, the key applications of hPSCs within the retinal field are described, including the use of these cells as developmental models, disease models, drug development, and finally, cell replacement therapies. In greater detail, the current report focuses on the differentiation of hPSC-derived RGCs and the many unique characteristics associated with these cells in vitro including their genetic identifiers, their electrophysiological activity, and their morphological maturation. Also described is the current progress in the use of patient-specific hPSCs to study optic neuropathies affecting RGCs, with emphasis on the use of these RGCs for studying disease mechanisms and pathogenesis, drug screening, and cell replacement therapies in future studies.

Keywords

hPSCs Retinal ganglion cells Pluripotent stem cells Retina Optic neuropathies 

Notes

Acknowledgments

Grant support was provided by the National Eye Institute (R01 EY024984 to JSM), Indiana Department of Health Brain and Spinal Cord Injury Fund (JSM), an IU Collaborative Research Grant from the Office of the Vice President for Research (JSM), an award from the IU Signature Center for Brain and Spinal Cord Injury (JSM), a grant from Stark Neurosciences Research Institute, Eli Lilly and Company, and by the Indiana Clinical and Translational Sciences Institute, funded in part by grant # UL1TR001108 from the National Institutes of Health, National Center for Advancing Translational Sciences (SO) and an IUPUI Graduate Office First Year University Fellowship (KL), and the Purdue Research Foundation Fellowship (KL).

Author Contributions: SO, KL, CF, ME, JM: manuscript writing; SO, KL, CF, EF: Data collection and figure design; SO, KL, CF, JM: manuscript revisions, JM: final approval of manuscript.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Sarah K. Ohlemacher
    • 1
  • Kirstin B. Langer
    • 1
  • Clarisse M. Fligor
    • 1
  • Elyse M. Feder
    • 1
  • Michael C. Edler
    • 1
    • 2
  • Jason S. Meyer
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of BiologyIndiana University Purdue University IndianapolisIndianapolisUSA
  2. 2.Department of Medical and Molecular GeneticsIndiana UniversityIndianapolisUSA
  3. 3.Stark Neurosciences Research InstituteIndiana UniversityIndianapolisUSA

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