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Pluripotent Stem Cells to Model Degenerative Retinal Diseases: The RPE Perspective

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Pluripotent Stem Cells in Eye Disease Therapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1186))

Abstract

Pluripotent stem cell technology, including human-induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs), has provided a suitable platform to investigate molecular and pathological alterations in an individual cell type using patient’s own cells. Importantly, hiPSCs/hESCs are amenable to genome editing providing unique access to isogenic controls. Specifically, the ability to introduce disease-causing mutations in control (unaffected) and conversely correct disease-causing mutations in patient-derived hiPSCs has provided a powerful approach to clearly link the disease phenotype with a specific gene mutation. In fact, utilizing hiPSC/hESC and CRISPR technology has provided significant insight into the pathomechanism of several diseases. With regard to the eye, the use of hiPSCs/hESCs to study human retinal diseases is especially relevant to retinal pigment epithelium (RPE)-based disorders. This is because several studies have now consistently shown that hiPSC-RPE in culture displays key physical, gene expression and functional attributes of human RPE in vivo. In this book chapter, we will discuss the current utility, limitations, and plausible future approaches of pluripotent stem cell technology for the study of retinal degenerative diseases. Of note, although we will broadly summarize the significant advances made in modeling and studying several retinal diseases utilizing hiPSCs/hESCs, our specific focus will be on the utility of patient-derived hiPSCs for (1) establishment of human cell models and (2) molecular and pharmacological studies on patient-derived cell models of retinal degenerative diseases where RPE cellular defects play a major pathogenic role in disease development and progression.

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  1. Sonal Dalvi and Chad A. Galloway contributed equally to this work.

Authors and Affiliations

  1. Department of Ophthalmology, Flaum Eye Institute, University of Rochester, Rochester, NY, USA

    Sonal Dalvi, Chad A. Galloway & Ruchira Singh

  2. Department of Biomedical Genetics, University of Rochester, Rochester, NY, USA

    Sonal Dalvi, Chad A. Galloway & Ruchira Singh

  3. UR Stem Cell and Regenerative Medicine Institute, Rochester, NY, USA

    Ruchira Singh

  4. Center for Visual Science, University of Rochester, Rochester, NY, USA

    Ruchira Singh

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  1. Sonal Dalvi
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  2. Chad A. Galloway
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  1. National Institutes of Health NEI, Bethesda, MD, USA

    Kapil Bharti

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Dalvi, S., Galloway, C.A., Singh, R. (2019). Pluripotent Stem Cells to Model Degenerative Retinal Diseases: The RPE Perspective. In: Bharti, K. (eds) Pluripotent Stem Cells in Eye Disease Therapy. Advances in Experimental Medicine and Biology, vol 1186. Springer, Cham. https://doi.org/10.1007/978-3-030-28471-8_1

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