Abstract
Age-related macular degeneration (AMD) is a highly prevalent irreversible impairment in the elderly population worldwide. Stem cell therapies have been considered potentially viable for treating AMD through the direct replacement of degenerated cells or secretion of trophic factors that facilitate the survival of existing cells. Among them, the safety of pluripotent stem cell-derived retinal pigment epithelial (RPE) cell transplantation against AMD, and some hereditary retinal degenerative diseases, has been discussed to a certain extent in clinical studies of RPE cell transplantation. Preparations are in progress for its clinical application. On the other hand, clinical trials using somatic stem cells are also being conducted, though these had controversial outcomes. Retinal regenerative medicine using stem cells is expected to make steady progress toward practical use while new technologies are incorporated from various fields, thereby making the role of ophthalmologists in this field increasingly important.
Highlights
Age-related macular degeneration (AMD) is one of the most common causes of blindness worldwide, especially in the elderly population
As a countermeasure to these problems, the transplanted cell source was reviewed, and we reported retinal pigment epithelium (RPE) cells derived from pluripotent stem cells (ES cells, iPS cells) as candidate graft cells [25,26,27]
We confirmed the proof of concept using the following steps: (1) The differentiated retinal sheets induced from ES/iPS cells via these culture systems were engrafted, resulting in maturation, while forming the entire structure of photoreceptor cells and maintaining reproducibility in all animal models [34,35,36,37]; (2) we demonstrated the possibility that photoreceptor cells in transplanted tissues form synapses with host bipolar cells using genetic labeling of synaptic markers and immunostaining; (3) functionally, after transplantation, the retinal ganglion cells of the host mouse and rat retina provide a photoresponse and photoreaction that is not seen in the untransplanted retina; (4) in addition, among blind mice with degenerated retina transplanted with mouse iPS cell-derived retinal sheets, a behavior test revealed that about 40% sensed the light after transplantation
Summary
Age-related macular degeneration (AMD) is one of the most common causes of blindness worldwide, especially in the elderly population. AMD patients are recommended to receive routine medical management, including antioxidant supplements and anti-vascular endothelial growth factor (anti-VEGF) agents. The former, including vitamins, lutein, and zeaxanthin, are applied to protect the retinal cells from oxidative stress. There are currently no effective methods for treating dry-type AMD. To address these problems, retinal cell therapy has attracted worldwide attention as the new era of treatment for retinal degenerative diseases [2,3,4,5], such as reconstruction and functional recovery of RPE by cell transplantation to maintain or restore visual function
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