Trends in Neurosciences
ReviewDevelopment of human embryonic stem cell therapies for age-related macular degeneration
Section snippets
Age-related macular degeneration and the retinal pigment epithelium
AMD is the most common cause of blindness in the developed world [1] and, with increasing life expectancy, the incidence of this disease is set only to increase in the future. Degeneration of macular photoreceptors leads to the loss of high-acuity central vision (Figure 1), which is required for fine detailed tasks, such as reading, driving, and recognising faces. The underlying cause of AMD stems from the loss of, or defects within, the RPE, a single monolayer of highly specialised cells found
Current and experimental treatments for AMD
Several treatments are available for patients with wet AMD, who account for approximately 10% of the total AMD population. Anti-VEGF treatments can stabilise wet AMD by reducing blood vessel growth and preventing further fluid accumulation 6, 7, whereas clinical treatments, such as surgical ablation of neovascular membranes, photodynamic therapy to seal leaky blood vessels or brachytherapy, where radiation therapy is used to destroy new vessels, can prevent progression of the disease. However,
Retinal degeneration and cell transplantation
Given the high number of patients with AMD and the length, complexity, and complications of the experimental surgical procedures described above, an ideal solution would utilise a preprepared source of tissue for transplant. Many possible cell types have been tested in an animal model of retinal degeneration, the Royal College of Surgeons (RCS) rat. Loss of vision in this animal is caused by a naturally occurring mutation in c-mer proto-oncogene tyrosine kinase (MERTK), a protein essential for
Human embryonic stem cells
In recent years, developments in ESC technologies have yielded novel sources of cells for use in AMD cellular therapy (Figure 4). HESCs have the potential to treat a variety of degenerative diseases and are an extremely attractive prospect for use in stem cell therapies owing to their ability to self-renew indefinitely while maintaining a stable undifferentiated state. HESCs can be isolated from the inner cell mass of the human blastocyst at approximately 5 days postfertilisation and maintained
iPSCs and RPE cell generation
iPSCs are stem cells derived from fully differentiated somatic cells, such as fibroblasts or blood cells. Somatic cells can be reprogrammed to pluripotency in vitro, typically using a combination of embryonic transcription factors 81, 82, 83 (Figure 4). iPSCs are similar to ESCs with regards to morphology, transcriptional profiling, pluripotency, and their potential to differentiate into the three germ layers [84]. The pluripotency of iPSCs has enabled researchers to differentiate reprogrammed
Acknowledgements
The authors would like to thank Shazeen Hasan and Sakina Gooljar for providing images of the HESC-RPE patch. This work was supported by funding from The London Project to Cure Blindness, The Medical Research Council (MRC) UK, The Californian Institute of Regenerative Medicine (CIRM), Fight for Sight UK, The Lincy Foundation, The Macular Society, and The National Institute for Health Research.
Glossary
- Differentiation
- commitment of a cell to a more specialised cell type.
- Drusen
- deposits of extracellular material (proteins and lipids) that form between the RPE and Bruch's membrane, which appear as distinct yellow–white spots. The exact etiology of this material is unknown. Although observed in normal ageing eyes, they are thought to be an early sign of macular degeneration.
- Embryonic stem cell (ESC)
- a pluripotent cell harvested from the inner cell mass of a pre-implantation embryo at the blastocyst
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