Development of human embryonic stem cell therapies for age-related macular degeneration

@article{Carr2013DevelopmentOH,
  title={Development of human embryonic stem cell therapies for age-related macular degeneration},
  author={Amanda-Jayne F. Carr and Matthew J. K. Smart and Conor M Ramsden and Michael B. Powner and Lyndon Da Cruz and P. J. Coffey},
  journal={Trends in Neurosciences},
  year={2013},
  volume={36},
  pages={385-395}
}
Age-related macular degeneration (AMD) is the leading cause of vision loss in older adults and ultimately leads to the death of photoreceptor cells in the macular area of the neural retina. Currently, treatments are only available for patients with the wet form of AMD. In this review, we describe recent approaches to develop cell-based therapies for the treatment of AMD. Recent research has focused on replacing the retinal pigment epithelium (RPE), a monolayer of cells vital to photoreceptor… Expand
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  • 2016
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References

SHOWING 1-10 OF 109 REFERENCES
Embryonic stem cell trials for macular degeneration: a preliminary report
TLDR
The first description of hESC-derived cells transplanted into human patients with Stargardt's macular dystrophy and dry age-related macular degeneration is provided, with no signs of hyperproliferation, tumorigenicity, ectopic tissue formation, or apparent rejection after 4 months. Expand
Molecular signature of primary retinal pigment epithelium and stem-cell-derived RPE cells.
TLDR
It is demonstrated that functional RPE cells can be derived from multiple lines of hESCs and hiPSCs with varying efficiencies and identified a set of 87 signature genes that are unique to human fRPE and a majority of these signature genes are shared by stem-cell-derived R PE cells. Expand
Protective Effects of Human iPS-Derived Retinal Pigment Epithelium Cell Transplantation in the Retinal Dystrophic Rat
TLDR
It is demonstrated that iPS cells can be differentiated into functional iPS-RPE and that transplantation of these cells can facilitate the short-term maintenance of photoreceptors through phagocytosis ofPhotoreceptor outer segments. Expand
Transplantation of the RPE in AMD
TLDR
Mechanisms leading to RPE dysfunction in aging and AMD are reviewed, laboratory studies on RPE transplantation, and surgical techniques used in AMD patients are reviewed. Expand
Human embryonic stem cell-derived cells rescue visual function in dystrophic RCS rats.
TLDR
Embryonic stem cells promise to provide a well-characterized and reproducible source of replacement tissue for human clinical studies and batches of RPE derived from NIH-approved hES cells were tested and shown capable of extensive photoreceptor rescue in an animal model of retinal disease. Expand
Molecular mechanisms of retinal pigment epithelium damage and development of age‐related macular degeneration
TLDR
This review discusses thoroughly RPE‐derived mechanisms in AMD pathology, and specific degenerative findings for AMD are accumulation of intracellular lysosomal lipofuscin and extracellular drusens. Expand
Directed differentiation of human embryonic stem cells into functional retinal pigment epithelium cells.
TLDR
It is demonstrated that nicotinamide promotes the differentiation of hESCs to neural and subsequently to RPE fate and factors from the TGF-beta superfamily, which presumably pattern RPE development during embryogenesis, further direct RPE differentiation. Expand
Embryonic stem cells and retinal repair
TLDR
This review examines the potential of embryonic stem cells for use in the treatment of retinal diseases involving photoreceptors and retinal pigment epithelium and considers both the potential barriers to transplant integration in the retina itself and the remodelling in host visual centres that is known to accompany retinal dystrophy. Expand
RPE transplantation and its role in retinal disease
TLDR
In the near future, refinements of current techniques are likely to allow RPE transplantation to enter the mainstream of retinal therapy at a time when the treatment of previously blinding retinal diseases is finally becoming a reality. Expand
Derivation of Functional Retinal Pigmented Epithelium from Induced Pluripotent Stem Cells
TLDR
iPSCs generated using Oct4, Sox2, Nanog, and Lin28 can spontaneously differentiate into RPE cells, which can then be isolated and cultured to form highly differentiated RPE monolayers, and further supports the finding that iPSCs are similar to hESCs in their differentiation potential. Expand
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5
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