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    Lab RGCs expanding opportunities for glaucoma research

    Research has implications for drug-screening study, pathways mediating progression

    Indianapolis—Researchers have successfully differentiated patient-derived induced pluripotent stem cells (iPSCs) into retinal ganglion cells (RGCs).

    Now, they are looking forward to using this approach to facilitate drug-screening studies and to characterize the pathogenic mechanisms of disease progression in optic neuropathies, said Jason S. Meyer, PhD.

    In a series of studies, the researchers first showed conclusively that cells derived from human PSCs were RGCs.

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    Then, through stepwise differentiation, they used skin fibroblasts harvested from a patient with glaucoma caused by a mutation in the Optineurin (OPTN) gene to generate RGCs, said Dr. Meyer, associate professor of biology, Indiana University Purdue University Indianapolis, and corresponding author of the paper [Ohlemacher SK, et al. Stem Cells. 2016;34:1553-1562].

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    Next, they showed that the OPTN glaucoma patient-derived RGCs could serve as an in vitro model of the disease and could be protected from undergoing degeneration when treated with drugs known to have neuroprotective properties.

    “Stem cell research involving differentiation of iPSCs is very appealing, because it lends itself to developing personalized medicine approaches,” Dr. Meyer said. “Although we and others previously showed iPSCs could be differentiated into cells with retinal characteristics that were presumably RGCs, our current study establishes the cells are truly RGCs.”

    More: How precision medicine is tracking glaucoma progression

    Furthermore, it is believed this work developing an in vitro model of glaucoma with patient-derived iPSCs opens the door to future research that will improve clinicians’ understanding of the pathways mediating progression of this blinding disease and finding new therapies through high-throughput drug screening, he noted.

    Proof that cells differentiated from human PSCs were RGCs was achieved through characterization of a variety of physiological, phenotypic, and morphological characteristics.

    Demonstration that the patient-derived iPSCS represented an in vitro model of glaucoma was based on evaluations showing that compared with RGCs derived from a nonglaucomatous control, they were much more likely to undergo apoptosis and degenerate, Dr. Meyer explained.

    Future application

    Cheryl Guttman Krader
    Cheryl Guttman is a medical writer based in Deerfield, Ill.

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