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Articles
Macular Degeneration: Cell Replacement vs Rescue
Cellular regeneration strategies for macular degeneration: past, present and future
- Valeria Chichagova,
- Dean Hallam,
- Joseph Collin,
- Darin Zerti,
- Birthe Dorgau,
- Majed Felemban,
- Majlinda Lako &
- David H. Steel
- Eyevolume 32, pages946–971 (2018)
- doi:10.1038/s41433-018-0061-z
- Download Citation
Received:29 November 2017Revised:05 January 2018Accepted:15 January 2018Published:05 March 2018
Abstract
Despite considerable effort and significant therapeutic advances, age-related macular degeneration (AMD) remains the commonest cause of blindness in the developed world. Progressive late-stage AMD with outer retinal degeneration currently has no proven treatment. There has been significant interest in the possibility that cellular treatments may slow or reverse visual loss in AMD. A number of modes of action have been suggested, including cell replacement and rescue, as well as immune modulation to delay the neurodegenerative process. Their appeal in this enigmatic disease relate to their generic, non-pathway-specific effects. The outer retina in particular has been at the forefront of developments in cellular regenerative therapies being surgically accessible, easily observable, as well as having a relatively simple architecture. Both the retinal pigment epithelium (RPE) and photoreceptors have been considered for replacement therapies as both sheets and cell suspensions. Studies using autologous RPE, and to a lesser extent, foetal retina, have shown proof of principle. A wide variety of cell sources have been proposed with pluripotent stem cell-derived cells currently holding the centre stage. Recent early-phase trials using these cells for RPE replacement have met safety endpoints and hinted at possible efficacy. Animal studies have confirmed the promise that photoreceptor replacement, even in a completely degenerated outer retina may restore some vision. Many challenges, however, remain, not least of which include avoiding immune rejection, ensuring long-term cellular survival and maximising effect. This review provides an overview of progress made, ongoing studies and challenges ahead.