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Retinal Ganglion Cells in a Dish: Current Strategies and Recommended Best Practices for Effective In Vitro Modeling of Development and Disease

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Human iPSC-derived Disease Models for Drug Discovery

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 281))

Abstract

The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem cells (hPSCs) provides an extraordinary opportunity to study the development of RGCs as well as cellular mechanisms underlying their degeneration in optic neuropathies. In the past several years, multiple approaches have been established that allow for the generation of RGCs from hPSCs, with these methods greatly improved in more recent studies to yield mature RGCs that more faithfully recapitulate phenotypes within the eye. Nevertheless, numerous differences still remain between hPSC-RGCs and those found within the human eye, with these differences likely explained at least in part due to the environment in which hPSC-RGCs are grown. With the ultimate goal of generating hPSC-RGCs that most closely resemble those within the retina for proper studies of retinal development, disease modeling, as well as cellular replacement, we review within this manuscript the current effective approaches for the differentiation of hPSC-RGCs, as well as how they have been applied for the investigation of RGC neurodegenerative diseases such as glaucoma. Furthermore, we provide our opinions on the characteristics of RGCs necessary for their use as effective in vitro disease models and importantly, how these current systems should be improved to more accurately reflect disease states. The establishment of characteristics in differentiated hPSC-RGCs that more effectively mimic RGCs within the retina will not only enable their use as effective models of RGC development, but will also create a better disease model for the identification of mechanisms underlying the neurodegeneration of RGCs in disease states such as glaucoma, further facilitating the development of therapeutic approaches to rescue RGCs from degeneration in disease states.

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Authors and Affiliations

  1. Department of Biology, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA

    Kang-Chieh Huang

  2. Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA

    Kang-Chieh Huang, Cátia Gomes & Jason S. Meyer

  3. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA

    Cátia Gomes & Jason S. Meyer

  4. Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA

    Jason S. Meyer

  5. Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, IN, USA

    Jason S. Meyer

Authors
  1. Kang-Chieh Huang
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  2. Cátia Gomes
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  3. Jason S. Meyer
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Correspondence to Jason S. Meyer .

Editor information

Editors and Affiliations

  1. Center for Prevention and Treatment of Visual Loss; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA

    Markus H. Kuehn

  2. School of Pharmacy, Qingdao University, Qingdao, Shandong, China

    Wei Zhu

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Huang, KC., Gomes, C., Meyer, J.S. (2023). Retinal Ganglion Cells in a Dish: Current Strategies and Recommended Best Practices for Effective In Vitro Modeling of Development and Disease. In: Kuehn, M.H., Zhu, W. (eds) Human iPSC-derived Disease Models for Drug Discovery. Handbook of Experimental Pharmacology, vol 281. Springer, Cham. https://doi.org/10.1007/164_2023_642

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