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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.<\/jats:p>","DOI":"10.1002\/stem.2356","type":"journal-article","created":{"date-parts":[[2016,3,21]],"date-time":"2016-03-21T05:07:55Z","timestamp":1458536875000},"page":"1553-1562","source":"Crossref","is-referenced-by-count":122,"title":["Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration"],"prefix":"10.1093","volume":"34","author":[{"given":"Sarah K.","family":"Ohlemacher","sequence":"first","affiliation":[{"name":"Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshayalakshmi","family":"Sridhar","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yucheng","family":"Xiao","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Hochstetler","sequence":"additional","affiliation":[{"name":"Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansoor","family":"Sarfarazi","sequence":"additional","affiliation":[{"name":"Molecular Ophthalmic Genetics Laboratory, University of Connecticut Health Center, Farmington, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore R.","family":"Cummins","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University, Indianapolis, IN, USA"},{"name":"Department of Pharmacology and Toxicology, 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