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Retinal Organoids: An Emerging Technology for Retinal Disease Research and Therapy

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Cellular Therapies for Retinal Disease

Abstract

Retinal cell replacement is a promising therapeutic approach to restore vision to millions of people worldwide. Three-dimensional culture methods can produce large numbers of human embryonic retinal cells from pluripotent stem cells (PSCs), stimulating optimism for clinical use. These cells develop in a tissue environment that recapitulates many aspects of development in vivo. Most notably, the retinal progenitor cells are competent to give rise to all major retinal cells types, which segregate to rudimentary retinal layers. The cells are expected to mimic their natural counterparts at the molecular level, but that has yet to be demonstrated. These methodologies can produce impressive embryonic retinal structures, but will require optimization before meeting clinical needs. Using current methods PSC-derived retinal organoids do not fully mature, suggesting that the in vitro environment does not reproduce that of late fetal development. However, studies to date suggest that immature photoreceptor or retinal ganglion cells, roughly those of mid-gestation, function best for transplantation. This developmental stage appears to be well reproduced in vitro, and therefore the PSC-derived retinal cells may be appropriate for cell replacement approaches. Three-dimensional culture methods using PSC-derived cells offer hope to better understand and treat retinal disease.

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Abbreviations

AMD:

Age-related macular degeneration

BMP:

Bone morphogenetic protein

ECM:

Extracellular matrix

FBS:

Fetal bovine serum

GFP:

Green fluorescent protein

hESC:

Human embryonic stem cell

hiPSC:

Human iPSC

ILM:

Inner limiting membrane

INL:

Inner nuclear layer

IPL:

Inner plexiform layer

iPSC:

Induced pluripotent stem cell

mESC:

Mouse embryonic stem cell

NR:

Neural retina

ONL:

Outer nuclear layer

OPL:

Outer plexiform layer

OV:

Optic vesicle

PSC:

Pluripotent stem cell

RP:

Retinitis pigmentosa

RPE:

Retinal pigment epithelium

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Acknowledgments

The authors acknowledge the generous support of the A.B. Reins Foundation, the Neonatal Blindness Research Fund, the Larry and Celia Moh Foundation, Research to Prevent Blindness, NIH National Eye Institute grant R21EY025419 (JGA & DC), and NIH grant T32HD060549 to the USC Keck School of Medicine Development, Stem Cells, and Regenerative Medicine Program (DWHS) during the preparation of this chapter.

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Authors and Affiliations

  1. Division of Ophthalmology, Department of Surgery, The Vision Center, Children’s Hospital Los Angeles, 4650 Sunset Blvd, MS 163, Los Angeles, CA, 90027, USA

    Jennifer G. Aparicio Ph.D., Dominic W. H. Shayler B.A. & David Cobrinik

  2. Development, Stem Cells, and Regenerative Medicine Program, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Dominic W. H. Shayler B.A. & David Cobrinik

  3. The Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    David Cobrinik

  4. Department of Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    David Cobrinik

  5. USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    David Cobrinik

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  1. Jennifer G. Aparicio Ph.D.
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  3. David Cobrinik
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Correspondence to Jennifer G. Aparicio Ph.D. .

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Editors and Affiliations

  1. Retina Division Chief; Department of Ophthalmology; Ahmanson Professor of Ophthalmology, Stein Eye Institute; David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    Steven D. Schwartz

  2. Retina Division; Department of Ophthalmology, Stein Eye Institute; David Geffen School of Medicine at UCLA, Los Angeles, California, USA

    Aaron Nagiel

  3. Head of Astellas Global Regenerative Medicine, Chief Scientific Officer at the Astellas Institute for Regenerative Medicine, Marlborough, Massachusetts, USA

    Robert Lanza

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Aparicio, J.G., Shayler, D.W.H., Cobrinik, D. (2017). Retinal Organoids: An Emerging Technology for Retinal Disease Research and Therapy. In: Schwartz, S., Nagiel, A., Lanza, R. (eds) Cellular Therapies for Retinal Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-49479-1_10

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