Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration

Sarah K. Ohlemacher, Akshayalakshmi Sridhar, Yucheng Xiao, Alexandra E. Hochstetler, Mansoor Sarfarazi, Theodore R. Cummins, Jason S. Meyer

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Human pluripotent stem cells (hPSCs), including both embryonic and induced pluripotent stem cells, possess the unique ability to readily differentiate into any cell type of the body, including cells of the retina. Although previous studies have demonstrated the ability to differentiate hPSCs to a retinal lineage, the ability to derive retinal ganglion cells (RGCs) from hPSCs has been complicated by the lack of specific markers with which to identify these cells from a pluripotent source. In the current study, the definitive identification of hPSC-derived RGCs was accomplished by their directed, stepwise differentiation through an enriched retinal progenitor intermediary, with resultant RGCs expressing a full complement of associated features and proper functional characteristics. These results served as the basis for the establishment of induced pluripotent stem cells (iPSCs) from a patient with a genetically inherited form of glaucoma, which results in damage and loss of RGCs. Patient-derived RGCs specifically exhibited a dramatic increase in apoptosis, similar to the targeted loss of RGCs in glaucoma, which was significantly rescued by the addition of candidate neuroprotective factors. Thus, the current study serves to establish a method by which to definitively acquire and identify RGCs from hPSCs and demonstrates the ability of hPSCs to serve as an effective in vitro model of disease progression. Moreover, iPSC-derived RGCs can be utilized for future drug screening approaches to identify targets for the treatment of glaucoma and other optic neuropathies.

Original languageEnglish (US)
JournalStem Cells
DOIs
StateAccepted/In press - 2016

Fingerprint

Pluripotent Stem Cells
Retinal Ganglion Cells
Induced Pluripotent Stem Cells
Glaucoma
Forensic Anthropology
Optic Nerve Diseases
Preclinical Drug Evaluations
Disease Progression
Retina
Apoptosis

Keywords

  • Differentiation
  • Glaucoma
  • Pluripotent stem cell
  • Retina
  • Retinal ganglion cell

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration. / Ohlemacher, Sarah K.; Sridhar, Akshayalakshmi; Xiao, Yucheng; Hochstetler, Alexandra E.; Sarfarazi, Mansoor; Cummins, Theodore R.; Meyer, Jason S.

In: Stem Cells, 2016.

Research output: Contribution to journalArticle

Ohlemacher, Sarah K. ; Sridhar, Akshayalakshmi ; Xiao, Yucheng ; Hochstetler, Alexandra E. ; Sarfarazi, Mansoor ; Cummins, Theodore R. ; Meyer, Jason S. / Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration. In: Stem Cells. 2016.
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