Stemming retinal regeneration with pluripotent stem cells …

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Cell replacement therapy is a promising treatment for irreversible retinal cell death in diverse diseases, such as age-related macular degeneration (AMD), Stargardt's disease, retinitis pigmentosa (RP) and glaucoma. These diseases are all characterized by the degeneration of one or two retinal cell types that cannot regenerate spontaneously in humans. Aberrant retinal pigment epithelial (RPE) cells can be observed through optical coherence tomography (OCT) in AMD patients. In RP patients, the morphological and functional abnormalities of RPE and photoreceptor layers are caused by a genetic abnormality. Stargardt's disease or juvenile macular degeneration, which is characterized by the loss of the RPE and photoreceptors in the macular area, causes central vision loss at an early age. Loss of retinal ganglion cells (RGCs) can be observed in patients with glaucoma. Once the retinal cell degeneration is triggered, no treatments can reverse it. Transplantation-based approaches have been proposed as a universal therapy to target patients with various concomitant diseases. Both the replacement of dead cells and neuroprotection are strategies used to rescue visual function in animal models of retinal degeneration. Diverse retinal cell types derived from pluripotent stem cells, including RPE cells, photoreceptors, RGCs and even retinal organoids with a layered structure, provide unlimited cell sources for transplantation. In addition, mesenchymal stem cells (MSCs) are multifunctional and protect degenerating retinal cells. The aim of this review is to summarize current findings from preclinical and clinical studies. We begin with a brief introduction to retinal degenerative diseases and cell death in diverse diseases, followed by methods for retinal cell generation. Preclinical and clinical studies are discussed, and future concerns about efficacy, safety and immunorejection are also addressed.

Retinal degeneration

Pluripotent stem cells

Retinal pigment epithelium

Stem cell-derived retinal cell

Retinal tissue


age-related macular degeneration

retinal pigment epithelial

retinal ganglion cells

mesenchymal stem cells

photoreceptor outer segment

pigment epithelium-derived factor

vascular endothelial growth factor

human embryonic stem cells

induced pluripotent stem cells

optical coherence tomography

visual evoked potential

adaptive optics scanning laser ophthalmoscopy

Toll-like receptor 3

genome-wide association analysis

retinal precursor cells

brain-derived neurotrophic factor

serum-free floating culture of embryoid body-like aggregates

hyaluronan and methylcellulose

regenerated wild Antheraeapernyi silk fibroin

human leukocyte antigen

outer limiting membrane

human Mller glia cells

inner segment/outer segment

adipose-derived stem cells

retinal pigment epithelial stem cells

central nervous system stem cells

membrane attack complexes

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2018 The Authors. Published by Elsevier Ltd.

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